AU2015204045A1 - Heteroaryl substituted nicotinamide compounds - Google Patents

Heteroaryl substituted nicotinamide compounds Download PDF

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Publication number: AU2015204045A1
Authority: AU; Australia
Prior art keywords: nicotinamide; pyridin; cyano; fluoro; hydroxy
Prior art date: 2014-01-03
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

AU2015204045A

Other languages

English (en)

Inventor

Piramanayagam ARUNACHALAM

John V. Duncia

Daniel S. Gardner

John Hynes

Sreekantha Ratna KUMAR

Natesan Murugesan

Satheesh Kesavan NAIR

Venkatram Reddy PAIDI

Joseph B. Santella

Kandhasamy SARKUNAM

Hong Wu

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Squibb Co

Original Assignee

Bristol Myers Squibb Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2014-01-03

Filing date

2015-01-02

Publication date

2016-08-18

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=52355270&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AU2015204045(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2015-01-02 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

2016-08-18 Publication of AU2015204045A1 publication Critical patent/AU2015204045A1/en

Status Abandoned legal-status Critical Current

Links

125000001072 heteroaryl group Chemical group 0.000 title claims abstract description 23
150000005480 nicotinamides Chemical class 0.000 title description 4
-1 pyrrolo[2,3-b]pyridinyl Chemical group 0.000 claims abstract description 279
150000001875 compounds Chemical class 0.000 claims abstract description 230
150000003839 salts Chemical class 0.000 claims abstract description 61
125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 27
125000001041 indolyl group Chemical group 0.000 claims abstract description 4
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims abstract description 4
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 734
235000005152 nicotinamide Nutrition 0.000 claims description 301
239000011570 nicotinamide Substances 0.000 claims description 301
229960003966 nicotinamide Drugs 0.000 claims description 301
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 149
125000000217 alkyl group Chemical group 0.000 claims description 111
125000001424 substituent group Chemical group 0.000 claims description 84
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 65
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 61
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 58
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 57
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 57
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 50
125000003566 oxetanyl group Chemical group 0.000 claims description 50
125000005466 alkylenyl group Chemical group 0.000 claims description 47
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 47
125000004093 cyano group Chemical group *C#N 0.000 claims description 43
125000002757 morpholinyl group Chemical group 0.000 claims description 38
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
201000010099 disease Diseases 0.000 claims description 31
125000000714 pyrimidinyl group Chemical group 0.000 claims description 28
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 27
229910052701 rubidium Inorganic materials 0.000 claims description 27
125000003709 fluoroalkyl group Chemical group 0.000 claims description 26
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 26
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 26
125000003386 piperidinyl group Chemical group 0.000 claims description 25
125000004076 pyridyl group Chemical group 0.000 claims description 25
229910052801 chlorine Inorganic materials 0.000 claims description 24
229910052731 fluorine Inorganic materials 0.000 claims description 24
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 22
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 20
125000002883 imidazolyl group Chemical group 0.000 claims description 20
FVDCNCNSRJWBDU-LBXVMSDZSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(3-hydroxycyclopentyl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC(CC2)O FVDCNCNSRJWBDU-LBXVMSDZSA-N 0.000 claims description 19
CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 19
229910052794 bromium Inorganic materials 0.000 claims description 18
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 18
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 17
239000008194 pharmaceutical composition Substances 0.000 claims description 17
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 17
125000002393 azetidinyl group Chemical group 0.000 claims description 16
125000004122 cyclic group Chemical group 0.000 claims description 16
229910052739 hydrogen Inorganic materials 0.000 claims description 16
VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 15
125000004193 piperazinyl group Chemical group 0.000 claims description 15
125000000753 cycloalkyl group Chemical group 0.000 claims description 13
IGVGARQHWLUJIO-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1,3-benzothiazol-2-amine Chemical compound C1C=CC=C2SC(N)NC21 IGVGARQHWLUJIO-UHFFFAOYSA-N 0.000 claims description 12
201000005569 Gout Diseases 0.000 claims description 12
NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 claims description 11
125000003545 alkoxy group Chemical group 0.000 claims description 10
NIZFPIBTGJOVRT-UHFFFAOYSA-N bicyclo[2.2.1]heptan-4-ol Chemical compound C1CC2CCC1(O)C2 NIZFPIBTGJOVRT-UHFFFAOYSA-N 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 10
BPHJXKPJAUOKCJ-GOSISDBHSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-methylcyclopropyl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2(CC2)C BPHJXKPJAUOKCJ-GOSISDBHSA-N 0.000 claims description 9
125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 9
208000027866 inflammatory disease Diseases 0.000 claims description 9
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 9
206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
AMTQAAAWXLVQBC-MRXNPFEDSA-N 1-[4-(ethylamino)-5-[[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]carbamoyl]pyridin-2-yl]pyrrolo[2,3-b]pyridine-5-carboxamide Chemical compound C(C)NC1=CC(=NC=C1C(NC[C@H](C(C)(C)O)F)=O)N1C=CC=2C1=NC=C(C2)C(=O)N AMTQAAAWXLVQBC-MRXNPFEDSA-N 0.000 claims description 8
208000023275 Autoimmune disease Diseases 0.000 claims description 8
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
239000003937 drug carrier Substances 0.000 claims description 8
125000000335 thiazolyl group Chemical group 0.000 claims description 8
FKEJGZSNPLZAOF-GOSISDBHSA-N 1-[4-(cyclobutylamino)-5-[[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]carbamoyl]pyridin-2-yl]pyrrolo[2,3-b]pyridine-5-carboxamide Chemical compound C1(CCC1)NC1=CC(=NC=C1C(NC[C@H](C(C)(C)O)F)=O)N1C=CC=2C1=NC=C(C2)C(=O)N FKEJGZSNPLZAOF-GOSISDBHSA-N 0.000 claims description 7
206010009900 Colitis ulcerative Diseases 0.000 claims description 7
OGEZLJGKMHUYIX-PVQCJRHBSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(1-fluoropropan-2-ylamino)-6-pyrrolo[2,3-d]pyrimidin-7-ylpyridine-3-carboxamide Chemical compound F[C@H](CNC(C1=CN=C(C=C1NC(CF)C)N1C=CC2=C1N=CN=C2)=O)C(C)(C)O OGEZLJGKMHUYIX-PVQCJRHBSA-N 0.000 claims description 7
201000006704 Ulcerative Colitis Diseases 0.000 claims description 7
125000006390 chloropyrimidinyl group Chemical group 0.000 claims description 7
125000004212 difluorophenyl group Chemical group 0.000 claims description 7
125000001207 fluorophenyl group Chemical group 0.000 claims description 7
201000006417 multiple sclerosis Diseases 0.000 claims description 7
125000002971 oxazolyl group Chemical group 0.000 claims description 7
125000003831 tetrazolyl group Chemical group 0.000 claims description 7
125000004306 triazinyl group Chemical group 0.000 claims description 7
125000001425 triazolyl group Chemical group 0.000 claims description 7
XIFYANZEZVMBFY-OTOKDRCRSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-(propan-2-ylamino)butyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)NC(C)C)F)C(=C2)NC(C)C XIFYANZEZVMBFY-OTOKDRCRSA-N 0.000 claims description 6
CJBBAOCEBITCOR-AFMYVXGZSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(3-fluorooxan-4-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2C(COCC2)F CJBBAOCEBITCOR-AFMYVXGZSA-N 0.000 claims description 6
208000011231 Crohn disease Diseases 0.000 claims description 6
JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 6
206010016207 Familial Mediterranean fever Diseases 0.000 claims description 6
206010018634 Gouty Arthritis Diseases 0.000 claims description 6
108010081348 HRT1 protein Hairy Proteins 0.000 claims description 6
102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 6
201000004681 Psoriasis Diseases 0.000 claims description 6
208000022993 cryopyrin-associated periodic syndrome Diseases 0.000 claims description 6
239000003085 diluting agent Substances 0.000 claims description 6
UHCBBWUQDAVSMS-UHFFFAOYSA-N fluoroethane Chemical compound CCF UHCBBWUQDAVSMS-UHFFFAOYSA-N 0.000 claims description 6
208000024908 graft versus host disease Diseases 0.000 claims description 6
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
HFRBZDDRCKXFEE-GOSISDBHSA-N 6-(5-chloropyrrolo[2,3-b]pyridin-1-yl)-4-(cyclobutylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CCC2 HFRBZDDRCKXFEE-GOSISDBHSA-N 0.000 claims description 5
QARKYDRRULREBY-QGZVFWFLSA-N 6-(5-chloropyrrolo[2,3-b]pyridin-1-yl)-4-(cyclopropylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC2 QARKYDRRULREBY-QGZVFWFLSA-N 0.000 claims description 5
QAZHCVDQTALKJV-MRXNPFEDSA-N 6-(5-chloropyrrolo[2,3-b]pyridin-1-yl)-4-(ethylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC QAZHCVDQTALKJV-MRXNPFEDSA-N 0.000 claims description 5
KXZCEDGLILHLAT-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C KXZCEDGLILHLAT-QGZVFWFLSA-N 0.000 claims description 5
CFEDNKIXNWADGG-GOSISDBHSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-4-(cyclopropylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC2 CFEDNKIXNWADGG-GOSISDBHSA-N 0.000 claims description 5
CMEAVEMZAITVDH-UHFFFAOYSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-(3-hydroxy-3-methylbutyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NCCC(C)(C)O)C(=C2)NC(C)C CMEAVEMZAITVDH-UHFFFAOYSA-N 0.000 claims description 5
JXDGDMWIHFLTKG-LJQANCHMSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(3-methyloxetan-3-yl)methylamino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC2(COC2)C JXDGDMWIHFLTKG-LJQANCHMSA-N 0.000 claims description 5
RCVGDDARVNZGSF-OZBJMMHXSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2S)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxan-3-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@@H](C(C)(C)O)F)C(=C2)NC2COCCC2 RCVGDDARVNZGSF-OZBJMMHXSA-N 0.000 claims description 5
MYDUROMSIMMXOY-SFHVURJKSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2S)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@@H](C(C)(C)O)F)C(=C2)NC(C)C MYDUROMSIMMXOY-SFHVURJKSA-N 0.000 claims description 5
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 5
208000009329 Graft vs Host Disease Diseases 0.000 claims description 5
208000006673 asthma Diseases 0.000 claims description 5
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 5
WTVNFKVGGUWHQC-UHFFFAOYSA-N decane-2,4-dione Chemical compound CCCCCCC(=O)CC(C)=O WTVNFKVGGUWHQC-UHFFFAOYSA-N 0.000 claims description 5
125000002098 pyridazinyl group Chemical group 0.000 claims description 5
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
201000000596 systemic lupus erythematosus Diseases 0.000 claims description 5
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 4
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
WMMDEXMMBNBYRX-JOCHJYFZSA-N 4-(1,3-benzothiazol-6-ylamino)-6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound S1C=NC2=C1C=C(C=C2)NC2=CC(=NC=C2C(=O)NC[C@H](C(C)(C)O)F)N2C=CC=1C2=NC=C(C1)C#N WMMDEXMMBNBYRX-JOCHJYFZSA-N 0.000 claims description 4
NPKYEULLEDSBTK-OAQYLSRUSA-N 4-(3-carbamoylanilino)-6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(N)(=O)C=1C=C(C=CC1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1C=CC=2C1=NC=C(C2)C#N NPKYEULLEDSBTK-OAQYLSRUSA-N 0.000 claims description 4
VDJALEYZVCZDBW-JOCHJYFZSA-N 4-(3-cyanoanilino)-6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC(=CC=C2)C#N VDJALEYZVCZDBW-JOCHJYFZSA-N 0.000 claims description 4
NSIOMQIXAYTWCZ-OAQYLSRUSA-N 4-(4-carbamoylanilino)-6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(N)(=O)C1=CC=C(C=C1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1C=CC=2C1=NC=C(C2)C#N NSIOMQIXAYTWCZ-OAQYLSRUSA-N 0.000 claims description 4
FCJKVKVZBVEKEK-MRXNPFEDSA-N 4-(cyclopropylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-(5-fluoropyrazolo[3,4-b]pyridin-1-yl)pyridine-3-carboxamide Chemical compound C1(CC1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1N=CC=2C1=NC=C(C2)F FCJKVKVZBVEKEK-MRXNPFEDSA-N 0.000 claims description 4
KMVCREJQMCAFTJ-OAHLLOKOSA-N 4-(cyclopropylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-pyrazolo[3,4-d]pyrimidin-1-ylpyridine-3-carboxamide Chemical compound C1(CC1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1N=CC=2C1=NC=NC2 KMVCREJQMCAFTJ-OAHLLOKOSA-N 0.000 claims description 4
MPCSWKAMAOGERT-MRXNPFEDSA-N 4-(cyclopropylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-pyrrolo[2,3-d]pyrimidin-7-ylpyridine-3-carboxamide Chemical compound C1(CC1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1C=CC2=C1N=CN=C2 MPCSWKAMAOGERT-MRXNPFEDSA-N 0.000 claims description 4
SXZNJGZYTHGZCA-MRXNPFEDSA-N 6-(5-bromopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound BrC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C SXZNJGZYTHGZCA-MRXNPFEDSA-N 0.000 claims description 4
UEAYPVSMYGCRQI-LJQANCHMSA-N 6-(5-chloroindol-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound ClC=1C=C2C=CN(C2=CC1)C1=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C1)NC(C)C UEAYPVSMYGCRQI-LJQANCHMSA-N 0.000 claims description 4
WRRIYXFCAYHKIM-UHFFFAOYSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-(2-morpholin-4-ylethyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCN1CCOCC1)C(=C2)NC(C)C WRRIYXFCAYHKIM-UHFFFAOYSA-N 0.000 claims description 4
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102000003298 tumor necrosis factor receptor Human genes 0.000 claims description 4
125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 claims description 3
UXOKRVWJKRLBSR-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(cyclopropylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC2 UXOKRVWJKRLBSR-QGZVFWFLSA-N 0.000 claims description 3
GHOYTVBLDYSILK-QGZVFWFLSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-4-(ethylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC GHOYTVBLDYSILK-QGZVFWFLSA-N 0.000 claims description 3
NDMKEYPCCUCEMZ-QGZVFWFLSA-N [(3R)-4-[[6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridine-3-carbonyl]amino]-3-fluoro-2-methylbutan-2-yl] dihydrogen phosphate Chemical compound P(=O)(OC(C)([C@@H](CNC(C1=CN=C(C=C1NC(C)C)N1N=CC=2C1=NC=C(C2)C#N)=O)F)C)(O)O NDMKEYPCCUCEMZ-QGZVFWFLSA-N 0.000 claims description 3
230000000737 periodic effect Effects 0.000 claims description 3
208000011580 syndromic disease Diseases 0.000 claims description 3
DQYRLGQECPTQCM-LRTDYKAYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxan-3-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2COCCC2 DQYRLGQECPTQCM-LRTDYKAYSA-N 0.000 claims description 2
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
208000005777 Lupus Nephritis Diseases 0.000 claims description 2
125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
206010025135 lupus erythematosus Diseases 0.000 claims description 2
208000004296 neuralgia Diseases 0.000 claims description 2
208000021722 neuropathic pain Diseases 0.000 claims description 2
238000002560 therapeutic procedure Methods 0.000 claims description 2
125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
MNBZCMUZKQJIJP-LBXVMSDZSA-N 4-[(3-aminocyclopentyl)amino]-6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound NC1CC(CC1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1C=CC=2C1=NC=C(C2)C#N MNBZCMUZKQJIJP-LBXVMSDZSA-N 0.000 claims 6
DYBZYXWEMQGBKG-LEHRNKBSSA-N 4-[(3-fluorocyclopentyl)amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-(5-fluoropyrazolo[3,4-b]pyridin-1-yl)pyridine-3-carboxamide Chemical compound FC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC(CC2)F DYBZYXWEMQGBKG-LEHRNKBSSA-N 0.000 claims 6
AHDQFUWGEYVKDP-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-fluoro-2-(3-hydroxyoxetan-3-yl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCC(C1(COC1)O)F)C(=C2)NC(C)C AHDQFUWGEYVKDP-UHFFFAOYSA-N 0.000 claims 5
JIHUQPSKFFAMQP-KPMSDPLLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[(3,3-difluorocyclopentyl)amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC(CC2)(F)F JIHUQPSKFFAMQP-KPMSDPLLSA-N 0.000 claims 4
FUGDNJSQRKMYJH-LADRWXRNSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[(3-fluorocyclopentyl)amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC(CC2)F FUGDNJSQRKMYJH-LADRWXRNSA-N 0.000 claims 4
KLBPPKOIYGZGRH-QLYHWAPBSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[(2S)-3-fluorobutan-2-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H](C)C(C)F KLBPPKOIYGZGRH-QLYHWAPBSA-N 0.000 claims 4
BNLCFNJSPRBWLJ-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(3-hydroxybutyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC(C)O)C(=C2)NC(C)C BNLCFNJSPRBWLJ-UHFFFAOYSA-N 0.000 claims 4
ZVCPDKYBRFNEPS-DIAVIDTQSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-4-methylpentyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C(C)C)O)F)C(=C2)NC(C)C ZVCPDKYBRFNEPS-DIAVIDTQSA-N 0.000 claims 4
JCVANOXNUKRWNN-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[1-(1-methylsulfonylazetidine-3-carbonyl)piperidin-4-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1CCN(CC1)C(=O)C1CN(C1)S(=O)(=O)C)C(=C2)NC(C)C JCVANOXNUKRWNN-UHFFFAOYSA-N 0.000 claims 4
KLMIIJJVCQXXEX-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[3-(methanesulfonamido)butyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC(C)NS(=O)(=O)C)C(=C2)NC(C)C KLMIIJJVCQXXEX-UHFFFAOYSA-N 0.000 claims 4
GYYUPSNZRMJWBT-QNSVNVJESA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-4-[(4,4-difluorooxolan-3-yl)amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2COCC2(F)F GYYUPSNZRMJWBT-QNSVNVJESA-N 0.000 claims 4
OIIBJHGQSMRLFM-OAQYLSRUSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(3-sulfamoylanilino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC(=CC=C2)S(N)(=O)=O OIIBJHGQSMRLFM-OAQYLSRUSA-N 0.000 claims 4
ZJFYOWHIXAWXEK-WIXQSORDSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[3-(2,2,2-trifluoroethylamino)cyclopentyl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC(CC2)NCC(F)(F)F ZJFYOWHIXAWXEK-WIXQSORDSA-N 0.000 claims 4
ADGJSGULIJNUIP-UHFFFAOYSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[2-fluoro-2-(3-hydroxyoxetan-3-yl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NCC(C1(COC1)O)F)C(=C2)NC(C)C ADGJSGULIJNUIP-UHFFFAOYSA-N 0.000 claims 4
VCQDIPHQOVIZME-UHFFFAOYSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[4-(1-cyclopropyl-1-hydroxyethyl)cyclohexyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC1CCC(CC1)C(C)(O)C1CC1)C(=C2)NC(C)C VCQDIPHQOVIZME-UHFFFAOYSA-N 0.000 claims 4
RHOQJZOHJOWYFT-JTTJXQCZSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-(5-fluoropyrazolo[3,4-b]pyridin-1-yl)-4-[(3-hydroxycyclopentyl)amino]pyridine-3-carboxamide Chemical compound FC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC(CC2)O RHOQJZOHJOWYFT-JTTJXQCZSA-N 0.000 claims 4
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 3
KDRKBTLUUIXZBU-LADRWXRNSA-N 4-[(3-aminocyclopentyl)amino]-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound NC1CC(CC1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1N=CC=2C1=NC=C(C2)C#N KDRKBTLUUIXZBU-LADRWXRNSA-N 0.000 claims 3
UAYXQFIOSGYLPW-XGWLTEMNSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(1R,2R)-2-(hydroxymethyl)cyclopropyl]amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2[C@@H](C2)CO UAYXQFIOSGYLPW-XGWLTEMNSA-N 0.000 claims 3
FDOZSXHRUCFSEP-HXUWFJFHSA-N 1-[4-(1,3-benzoxazol-6-ylamino)-5-[[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]carbamoyl]pyridin-2-yl]pyrazolo[3,4-b]pyridine-5-carboxamide Chemical compound O1C=NC2=C1C=C(C=C2)NC2=CC(=NC=C2C(NC[C@H](C(C)(C)O)F)=O)N2N=CC=1C2=NC=C(C1)C(=O)N FDOZSXHRUCFSEP-HXUWFJFHSA-N 0.000 claims 2
TURYFHROMWPGCU-GOSISDBHSA-N 1-[4-(azetidin-3-ylmethylamino)-5-[[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]carbamoyl]pyridin-2-yl]pyrrolo[2,3-b]pyridine-5-carboxamide Chemical compound N1CC(C1)CNC1=CC(=NC=C1C(NC[C@H](C(C)(C)O)F)=O)N1C=CC=2C1=NC=C(C2)C(=O)N TURYFHROMWPGCU-GOSISDBHSA-N 0.000 claims 2
PABHAGKYDXMMJH-JOCHJYFZSA-N 2-methylpropyl N-[[1-[5-[[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]carbamoyl]-4-(propan-2-ylamino)pyridin-2-yl]pyrrolo[2,3-b]pyridin-5-yl]methyl]carbamate Chemical compound F[C@H](CNC(=O)C=1C(=CC(=NC1)N1C=CC=2C1=NC=C(C2)CNC(OCC(C)C)=O)NC(C)C)C(C)(C)O PABHAGKYDXMMJH-JOCHJYFZSA-N 0.000 claims 2
GSMHQIQNGMGOCR-OAQYLSRUSA-N 4-(1,3-benzothiazol-6-ylamino)-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound S1C=NC2=C1C=C(C=C2)NC2=CC(=NC=C2C(=O)NC[C@H](C(C)(C)O)F)N2N=CC=1C2=NC=C(C1)C#N GSMHQIQNGMGOCR-OAQYLSRUSA-N 0.000 claims 2
MGEBHJVSXLZMEG-JOCHJYFZSA-N 4-(1,3-benzoxazol-6-ylamino)-6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound O1C=NC2=C1C=C(C=C2)NC2=CC(=NC=C2C(=O)NC[C@H](C(C)(C)O)F)N2C=CC=1C2=NC=C(C1)C#N MGEBHJVSXLZMEG-JOCHJYFZSA-N 0.000 claims 2
DGIAYHGMUTXKBW-OAQYLSRUSA-N 4-(2H-benzotriazol-5-ylamino)-6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound N1N=NC2=C1C=C(C=C2)NC2=CC(=NC=C2C(=O)NC[C@H](C(C)(C)O)F)N2C=CC=1C2=NC=C(C1)C#N DGIAYHGMUTXKBW-OAQYLSRUSA-N 0.000 claims 2
QYBKXEZMPUWSPR-HXUWFJFHSA-N 4-(3-cyano-2-fluoroanilino)-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=C(C(=CC=C2)C#N)F QYBKXEZMPUWSPR-HXUWFJFHSA-N 0.000 claims 2
SFLUKXBMSPRQKP-OAQYLSRUSA-N 4-(3-cyano-2-fluoroanilino)-6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=C(C(=CC=C2)C#N)F SFLUKXBMSPRQKP-OAQYLSRUSA-N 0.000 claims 2
CJVXJLZTOYLJLW-OAQYLSRUSA-N 4-(3-cyanoanilino)-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC(=CC=C2)C#N CJVXJLZTOYLJLW-OAQYLSRUSA-N 0.000 claims 2
WGXLIILNAYHYAL-OAQYLSRUSA-N 4-(4-cyanoanilino)-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC=C(C=C2)C#N WGXLIILNAYHYAL-OAQYLSRUSA-N 0.000 claims 2
SQEVLRXBGGYTTA-UHFFFAOYSA-N 4-(tert-butylamino)-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(3-fluoro-3-methylbutyl)pyridine-3-carboxamide Chemical compound C(C)(C)(C)NC1=CC(=NC=C1C(=O)NCCC(C)(C)F)N1N=CC=2C1=NC=C(C2)C#N SQEVLRXBGGYTTA-UHFFFAOYSA-N 0.000 claims 2
XXHNMBSJJKQQHK-QGZVFWFLSA-N 4-(tert-butylamino)-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(C)(C)(C)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1N=CC=2C1=NC=C(C2)C#N XXHNMBSJJKQQHK-QGZVFWFLSA-N 0.000 claims 2
UAYADTMIZAGMIX-HXUWFJFHSA-N 4-[(1-acetylazetidin-3-yl)amino]-6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(C)(=O)N1CC(C1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1C=CC=2C1=NC=C(C2)C#N UAYADTMIZAGMIX-HXUWFJFHSA-N 0.000 claims 2
ZEJBDLQGWRFURY-GOSISDBHSA-N 4-[(3-amino-2,2-dimethylpropyl)amino]-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound NCC(CNC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1N=CC=2C1=NC=C(C2)C#N)(C)C ZEJBDLQGWRFURY-GOSISDBHSA-N 0.000 claims 2
MDZLMPSQMGFHSW-FZKQIMNGSA-N 4-[[(2R)-butan-2-yl]amino]-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound [C@@H](C)(CC)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1N=CC=2C1=NC=C(C2)C#N MDZLMPSQMGFHSW-FZKQIMNGSA-N 0.000 claims 2
MDZLMPSQMGFHSW-SCLBCKFNSA-N 4-[[(2S)-butan-2-yl]amino]-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound [C@H](C)(CC)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1N=CC=2C1=NC=C(C2)C#N MDZLMPSQMGFHSW-SCLBCKFNSA-N 0.000 claims 2
VYBXBZJGLGCODE-WIYYLYMNSA-N 4-[[(3R)-1-(2-cyanoacetyl)pyrrolidin-3-yl]amino]-6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2CN(CC2)C(CC#N)=O VYBXBZJGLGCODE-WIYYLYMNSA-N 0.000 claims 2
RIKJADQAUBEMBM-QGZVFWFLSA-N 4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-(5-fluoropyrazolo[3,4-b]pyridin-1-yl)pyridine-3-carboxamide Chemical compound FC(CN1N=CC(=C1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1N=CC=2C1=NC=C(C2)F)F RIKJADQAUBEMBM-QGZVFWFLSA-N 0.000 claims 2
AOXMXXVBXOFOHR-HXUWFJFHSA-N 4-[[1-(2-cyanoethyl)pyrazol-4-yl]amino]-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCC#N AOXMXXVBXOFOHR-HXUWFJFHSA-N 0.000 claims 2
VIZZPTHAPDMHQW-CQSZACIVSA-N 6-(2-aminopurin-9-yl)-N-[(2R)-2,3-difluoro-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=NC=C2N=CN(C2=N1)C1=NC=C(C(=O)NC[C@H](C(C)(C)F)F)C(=C1)NC(C)C VIZZPTHAPDMHQW-CQSZACIVSA-N 0.000 claims 2
ZYFYMVODNZNXCC-MRXNPFEDSA-N 6-(5-amino-6-cyanoimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C)C#N ZYFYMVODNZNXCC-MRXNPFEDSA-N 0.000 claims 2
NYYBKXVMRIAOFQ-RHSMWYFYSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-4-[[(2R)-2-fluorobutyl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC[C@@H](CC)F NYYBKXVMRIAOFQ-RHSMWYFYSA-N 0.000 claims 2
YCWXXNCLYYNMMU-GOSISDBHSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoropropyl)pyrazol-4-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(C)(F)F YCWXXNCLYYNMMU-GOSISDBHSA-N 0.000 claims 2
QRYOKDRMUWRCNC-LJQANCHMSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2-cyanoethyl)pyrazol-4-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCC#N QRYOKDRMUWRCNC-LJQANCHMSA-N 0.000 claims 2
QVJDDRIJMROONU-MRXNPFEDSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-4-[[2-(difluoromethoxy)-2-methylpropyl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC(C)(C)OC(F)F QVJDDRIJMROONU-MRXNPFEDSA-N 0.000 claims 2
HWPJPHASWPXBPQ-MRXNPFEDSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2,3-difluoro-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)F)F)C(=C2)NC(C)C HWPJPHASWPXBPQ-MRXNPFEDSA-N 0.000 claims 2
KEMUCYRFZZIBDV-GOSISDBHSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxan-4-ylamino)pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CCOCC2 KEMUCYRFZZIBDV-GOSISDBHSA-N 0.000 claims 2
XBAVFUADMAKJPD-MRXNPFEDSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2COC2 XBAVFUADMAKJPD-MRXNPFEDSA-N 0.000 claims 2
IOIZZRPAGUPGLO-LJQANCHMSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-propan-2-ylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)C(C)C IOIZZRPAGUPGLO-LJQANCHMSA-N 0.000 claims 2
OKPCCXXZYTXSOP-LJQANCHMSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-propylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCC OKPCCXXZYTXSOP-LJQANCHMSA-N 0.000 claims 2
JBMSAMOLSRLBBB-QRWMCTBCSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(2-hydroxy-3-methylbutyl)amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC(C(C)C)O JBMSAMOLSRLBBB-QRWMCTBCSA-N 0.000 claims 2
XHFWDOMTYDGSAY-WMLDXEAASA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2S)-1-hydroxybutan-2-yl]amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H](CO)CC XHFWDOMTYDGSAY-WMLDXEAASA-N 0.000 claims 2
OBGHRBOKXNOHPI-QGZVFWFLSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(F)(F)F OBGHRBOKXNOHPI-QGZVFWFLSA-N 0.000 claims 2
HXYJSCGJGOVVRR-LJQANCHMSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2-methoxyethyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCOC HXYJSCGJGOVVRR-LJQANCHMSA-N 0.000 claims 2
LEFVETSDWIDJMU-UHFFFAOYSA-N 6-(5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[2-fluoro-2-(3-hydroxyoxetan-3-yl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCC(C1(COC1)O)F)C(=C2)NC(C)C LEFVETSDWIDJMU-UHFFFAOYSA-N 0.000 claims 2
XANBFOVLWAGFMY-QGZVFWFLSA-N 6-(5-chloropyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C XANBFOVLWAGFMY-QGZVFWFLSA-N 0.000 claims 2
OCRNYQQQLWBSHB-GOSISDBHSA-N 6-(5-cyano-2,3-dihydropyrrolo[2,3-b]pyridin-1-yl)-4-(cyclopropylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(CC2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC2 OCRNYQQQLWBSHB-GOSISDBHSA-N 0.000 claims 2
GKYDWSONRCAFSB-GOSISDBHSA-N 6-(5-cyano-2,3-dihydropyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(CC2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2COC2 GKYDWSONRCAFSB-GOSISDBHSA-N 0.000 claims 2
XDROLSLUXFOACX-GOSISDBHSA-N 6-(5-cyano-2,3-dihydropyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(CC2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C XDROLSLUXFOACX-GOSISDBHSA-N 0.000 claims 2
YXHKRWBNALTLAO-OAHLLOKOSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(2,2-difluoroethylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC(F)F YXHKRWBNALTLAO-OAHLLOKOSA-N 0.000 claims 2
MMCPAMSQUGNPML-GOSISDBHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(2,2-dimethylpropylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC(C)(C)C MMCPAMSQUGNPML-GOSISDBHSA-N 0.000 claims 2
WVPPXMISHWHDSQ-PQJIZZRHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(3-fluorobutylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCC(C)F WVPPXMISHWHDSQ-PQJIZZRHSA-N 0.000 claims 2
JDRHSNGKRVLBQF-PQJIZZRHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(4-fluorobutan-2-ylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)CCF JDRHSNGKRVLBQF-PQJIZZRHSA-N 0.000 claims 2
BHOCTINCNBKMBD-GOSISDBHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(cyclopropylmethylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC2CC2 BHOCTINCNBKMBD-GOSISDBHSA-N 0.000 claims 2
AAXBXPGVRRKMPI-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)-N-(1-propan-2-ylsulfonylpiperidin-4-yl)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1CCN(CC1)S(=O)(=O)C(C)C)C(=C2)NC(C)C AAXBXPGVRRKMPI-UHFFFAOYSA-N 0.000 claims 2
QAELJMIRDBOASW-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)-N-(1-pyrimidin-2-ylpiperidin-4-yl)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1CCN(CC1)C1=NC=CC=N1)C(=C2)NC(C)C QAELJMIRDBOASW-UHFFFAOYSA-N 0.000 claims 2
OTUBVOKGHKVPGM-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)-N-(1H-pyrrolo[2,3-c]pyridin-5-yl)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC=1C=C3C(=CN1)NC=C3)C(=C2)NC(C)C OTUBVOKGHKVPGM-UHFFFAOYSA-N 0.000 claims 2
KGNYBYULAFTJGU-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)-N-(2-pyridin-4-ylethyl)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1=CC=NC=C1)C(=C2)NC(C)C KGNYBYULAFTJGU-UHFFFAOYSA-N 0.000 claims 2
XMWCDZXBAFFDAE-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)-N-(2H-tetrazol-5-ylmethyl)pyridine-3-carboxamide Chemical compound N=1NN=NC1CNC(C1=CN=C(C=C1NC(C)C)N1N=CC=2C1=NC=C(C2)C#N)=O XMWCDZXBAFFDAE-UHFFFAOYSA-N 0.000 claims 2
CGQRHQFGBXPGOS-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)-N-[1-(propan-2-ylsulfamoyl)piperidin-4-yl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1CCN(CC1)S(NC(C)C)(=O)=O)C(=C2)NC(C)C CGQRHQFGBXPGOS-UHFFFAOYSA-N 0.000 claims 2
RJEIMIKKJFIOOE-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)-N-[2-(4-sulfamoylphenyl)ethyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1=CC=C(C=C1)S(N)(=O)=O)C(=C2)NC(C)C RJEIMIKKJFIOOE-UHFFFAOYSA-N 0.000 claims 2
KHFFGYYIMYNNHH-LJQANCHMSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[(1-ethylpyrazol-4-yl)amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC KHFFGYYIMYNNHH-LJQANCHMSA-N 0.000 claims 2
FUBSJWBVYIDELJ-GOSISDBHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[(1-fluorocyclobutyl)methylamino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC2(CCC2)F FUBSJWBVYIDELJ-GOSISDBHSA-N 0.000 claims 2
RNBOHPGJVWATMT-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[(2,2-difluoro-3-hydroxy-3-methylbutyl)amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC(C(C)(C)O)(F)F RNBOHPGJVWATMT-QGZVFWFLSA-N 0.000 claims 2
WHAIRRCGWUFOEV-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[(3,3-difluorocyclobutyl)amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC(C2)(F)F WHAIRRCGWUFOEV-QGZVFWFLSA-N 0.000 claims 2
BLEARHDTMMELNN-TZHYSIJRSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[(4,4-difluorooxolan-3-yl)amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2COCC2(F)F BLEARHDTMMELNN-TZHYSIJRSA-N 0.000 claims 2
QJMOOBQGTLZTTP-LJQANCHMSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC(=NN2)C2CC2 QJMOOBQGTLZTTP-LJQANCHMSA-N 0.000 claims 2
APTQOGKWVSMUHG-MRXNPFEDSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[2-(difluoromethoxy)ethylamino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCOC(F)F APTQOGKWVSMUHG-MRXNPFEDSA-N 0.000 claims 2
NZKFSOJCIGTZNS-AWEZNQCLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[(2S)-1-hydroxypropan-2-yl]amino]-N-(3-methylbutyl)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC(C)C)C(=C2)N[C@H](CO)C NZKFSOJCIGTZNS-AWEZNQCLSA-N 0.000 claims 2
KGRQMJWKNWYSEO-NTKDMRAZSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[(3R)-1-(2,4-difluorobenzoyl)pyrrolidin-3-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2CN(CC2)C(C2=C(C=C(C=C2)F)F)=O KGRQMJWKNWYSEO-NTKDMRAZSA-N 0.000 claims 2
DPMLSZOFHFPNHM-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-3-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=NN(C=C2)CC(F)F DPMLSZOFHFPNHM-QGZVFWFLSA-N 0.000 claims 2
TUWXJJNZNDJPBJ-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-(2,2-difluoro-3-hydroxy-3-methylbutyl)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCC(C(C)(C)O)(F)F)C(=C2)NC=2C=NN(C2)CC(F)F TUWXJJNZNDJPBJ-UHFFFAOYSA-N 0.000 claims 2
LXUNUETVEDUWIX-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-(2-ethoxyethyl)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCOCC)C(=C2)NC=2C=NN(C2)CC(F)F LXUNUETVEDUWIX-UHFFFAOYSA-N 0.000 claims 2
NKWQECORFHBKHI-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-(2-methylpropyl)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCC(C)C)C(=C2)NC=2C=NN(C2)CC(F)F NKWQECORFHBKHI-UHFFFAOYSA-N 0.000 claims 2
KCYJWUITTHENPY-GOSISDBHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-[(2R)-2,3-difluoro-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)F)F)C(=C2)NC=2C=NN(C2)CC(F)F KCYJWUITTHENPY-GOSISDBHSA-N 0.000 claims 2
IBOZZZSAWUVNEQ-GOSISDBHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(F)F IBOZZZSAWUVNEQ-GOSISDBHSA-N 0.000 claims 2
NHQDSFFPKOOMSV-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-ethylpyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCC)C(=C2)NC=2C=NN(C2)CC(F)F NHQDSFFPKOOMSV-UHFFFAOYSA-N 0.000 claims 2
DXXMEKWNVCWOGJ-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-propan-2-ylpyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC(C)C)C(=C2)NC=2C=NN(C2)CC(F)F DXXMEKWNVCWOGJ-UHFFFAOYSA-N 0.000 claims 2
QIDDWZFSQVWYFM-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-propylpyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC)C(=C2)NC=2C=NN(C2)CC(F)F QIDDWZFSQVWYFM-UHFFFAOYSA-N 0.000 claims 2
XGUJOPJORCKOHJ-LJQANCHMSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoropropyl)pyrazol-4-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(C)(F)F XGUJOPJORCKOHJ-LJQANCHMSA-N 0.000 claims 2
MNCRDFOGPJRZIT-LJQANCHMSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(ethylcarbamoyl)pyrazol-4-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)C(NCC)=O MNCRDFOGPJRZIT-LJQANCHMSA-N 0.000 claims 2
QJWHSXBMJPEHRK-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[2-(difluoromethoxy)-2-methylpropyl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC(C)(C)OC(F)F QJWHSXBMJPEHRK-QGZVFWFLSA-N 0.000 claims 2
GYBPJJYUZIQFIO-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(1-ethylsulfonylpiperidin-4-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1CCN(CC1)S(=O)(=O)CC)C(=C2)NC(C)C GYBPJJYUZIQFIO-UHFFFAOYSA-N 0.000 claims 2
AYXVFXQHYMLPMP-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(2-cyclopropylethyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1CC1)C(=C2)NC(C)C AYXVFXQHYMLPMP-UHFFFAOYSA-N 0.000 claims 2
YAYCHJSCRZWZBV-ZDUSSCGKSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(2-cyclopropylethyl)-4-[[(2S)-1-hydroxypropan-2-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1CC1)C(=C2)N[C@H](CO)C YAYCHJSCRZWZBV-ZDUSSCGKSA-N 0.000 claims 2
XZCQSAOFWZLLEK-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(2-diethoxyphosphorylethyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCP(OCC)(OCC)=O)C(=C2)NC(C)C XZCQSAOFWZLLEK-UHFFFAOYSA-N 0.000 claims 2
KPCAXQRCUFPLEW-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(2-morpholin-4-yl-2-oxoethyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCC(=O)N1CCOCC1)C(=C2)NC(C)C KPCAXQRCUFPLEW-UHFFFAOYSA-N 0.000 claims 2
BGQVATYVDYCQCS-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(2-morpholin-4-ylethyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCN1CCOCC1)C(=C2)NC(C)C BGQVATYVDYCQCS-UHFFFAOYSA-N 0.000 claims 2
SNEXXOCGKCIIEI-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(2-morpholin-4-ylpyrimidin-5-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC=1C=NC(=NC1)N1CCOCC1)C(=C2)NC(C)C SNEXXOCGKCIIEI-UHFFFAOYSA-N 0.000 claims 2
TXQDWBPBEVGDTJ-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(3,3-difluorobutyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC(C)(F)F)C(=C2)NC(C)C TXQDWBPBEVGDTJ-UHFFFAOYSA-N 0.000 claims 2
YXXQOSPDXBXADA-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(3-hydroxy-3-methylbutyl)-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC(C)(C)O)C(=C2)NC2COC2 YXXQOSPDXBXADA-UHFFFAOYSA-N 0.000 claims 2
QIORAKXQKNWQFL-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(3-methylbutyl)-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC(C)C)C(=C2)NC2COC2 QIORAKXQKNWQFL-UHFFFAOYSA-N 0.000 claims 2
IOZZKWZMFYYMOE-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(3-methylbutyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC(C)C)C(=C2)NC(C)C IOZZKWZMFYYMOE-UHFFFAOYSA-N 0.000 claims 2
JKVJVIPHFJAORR-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(3-morpholin-4-ylpropyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCCN1CCOCC1)C(=C2)NC(C)C JKVJVIPHFJAORR-UHFFFAOYSA-N 0.000 claims 2
DMNCPHDWXCSHLZ-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(4-methoxycyclohexyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1CCC(CC1)OC)C(=C2)NC(C)C DMNCPHDWXCSHLZ-UHFFFAOYSA-N 0.000 claims 2
CFFZHDUGKQPNDU-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(4-morpholin-4-ylphenyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1=CC=C(C=C1)N1CCOCC1)C(=C2)NC(C)C CFFZHDUGKQPNDU-UHFFFAOYSA-N 0.000 claims 2
IXKTUGRQUSWDQK-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(5-hydroxypyridin-2-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1=NC=C(C=C1)O)C(=C2)NC(C)C IXKTUGRQUSWDQK-UHFFFAOYSA-N 0.000 claims 2
VVTJFOKYJXPFLI-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(5-methoxypyrazin-2-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1=NC=C(N=C1)OC)C(=C2)NC(C)C VVTJFOKYJXPFLI-UHFFFAOYSA-N 0.000 claims 2
TXXZJTQDYJOAQS-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(5-morpholin-4-ylpyridin-2-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1=NC=C(C=C1)N1CCOCC1)C(=C2)NC(C)C TXXZJTQDYJOAQS-UHFFFAOYSA-N 0.000 claims 2
QJGUPCQWEFDKSQ-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(6-morpholin-4-ylpyridin-3-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC=1C=NC(=CC1)N1CCOCC1)C(=C2)NC(C)C QJGUPCQWEFDKSQ-UHFFFAOYSA-N 0.000 claims 2
LXYSEDXJTKGDDP-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(6-piperazin-1-ylpyridin-3-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC=1C=NC(=CC1)N1CCNCC1)C(=C2)NC(C)C LXYSEDXJTKGDDP-UHFFFAOYSA-N 0.000 claims 2
KKHZVTSZTXMDKG-ROUUACIJSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(1S,3S)-3-(2-hydroxypropan-2-yl)cyclopentyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)N[C@@H]1C[C@H](CC1)C(C)(C)O)C(=C2)NC(C)C KKHZVTSZTXMDKG-ROUUACIJSA-N 0.000 claims 2
IVRPGQJLUKENDQ-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2,3-difluoro-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)F)F)C(=C2)NC(C)C IVRPGQJLUKENDQ-QGZVFWFLSA-N 0.000 claims 2
PEVHGVCWWGBSBT-OAQYLSRUSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2,3-difluoro-3-methylbutyl]-4-[4-(1-methyltetrazol-5-yl)anilino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)F)F)C(=C2)NC2=CC=C(C=C2)C2=NN=NN2C PEVHGVCWWGBSBT-OAQYLSRUSA-N 0.000 claims 2
OBRJOEWIXBNRHD-OAHLLOKOSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-(methylamino)-3-oxopropyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(=O)NC)F)C(=C2)NC(C)C OBRJOEWIXBNRHD-OAHLLOKOSA-N 0.000 claims 2
QGMAWAIXVBYBNC-GOSISDBHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(1,3-oxazol-4-ylmethylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC=2N=COC2 QGMAWAIXVBYBNC-GOSISDBHSA-N 0.000 claims 2
MKSBFTKWAJAAAD-MRXNPFEDSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(3,3,3-trifluoropropylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCC(F)(F)F MKSBFTKWAJAAAD-MRXNPFEDSA-N 0.000 claims 2
OOZDTSMYWIRWSE-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(3-fluoropropylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCCF OOZDTSMYWIRWSE-QGZVFWFLSA-N 0.000 claims 2
YWLITVFFGZSXAO-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2COC2 YWLITVFFGZSXAO-QGZVFWFLSA-N 0.000 claims 2
WKMZLWVHEDDZNQ-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCC WKMZLWVHEDDZNQ-QGZVFWFLSA-N 0.000 claims 2
LOJSKXGPWGSSDI-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-hydroxy-2-methylpropan-2-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(CO)(C)C LOJSKXGPWGSSDI-QGZVFWFLSA-N 0.000 claims 2
UFBMVIBCQYKJKH-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-methylcyclopropyl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2(CC2)C UFBMVIBCQYKJKH-QGZVFWFLSA-N 0.000 claims 2
OEYYOVDYZPNDOJ-GOSISDBHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-methylsulfonylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)S(=O)(=O)C OEYYOVDYZPNDOJ-GOSISDBHSA-N 0.000 claims 2
VSHJFMQCLSSKPU-RUZDIDTESA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-phenylpiperidin-4-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CCN(CC2)C2=CC=CC=C2 VSHJFMQCLSSKPU-RUZDIDTESA-N 0.000 claims 2
PKOSDQDNBPVSMM-HXUWFJFHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-propylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCC PKOSDQDNBPVSMM-HXUWFJFHSA-N 0.000 claims 2
CVZOBSKWFTWVCV-PLEWWHCXSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(2-fluoro-3-hydroxy-2-methylpropyl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC(CO)(C)F CVZOBSKWFTWVCV-PLEWWHCXSA-N 0.000 claims 2
RRXFLYINENEJFU-MUMRKEEXSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(2-hydroxy-3-methylbutyl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC(C(C)C)O RRXFLYINENEJFU-MUMRKEEXSA-N 0.000 claims 2
LYNKSXRGULDXFV-GOSISDBHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(2-methoxy-2-methylpropyl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC(C)(C)OC LYNKSXRGULDXFV-GOSISDBHSA-N 0.000 claims 2
OHOHYAKWIVIRIT-OAQYLSRUSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(2-methyl-2-morpholin-4-ylpropyl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC(C)(N2CCOCC2)C OHOHYAKWIVIRIT-OAQYLSRUSA-N 0.000 claims 2
YOLPFNYXENQSIE-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(2-methylpyrazol-3-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC=NN2C YOLPFNYXENQSIE-QGZVFWFLSA-N 0.000 claims 2
BBRBXBJSYCNPEI-GOSISDBHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(3-fluoro-3-methylbutyl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCC(C)(C)F BBRBXBJSYCNPEI-GOSISDBHSA-N 0.000 claims 2
HAOFFINFSLFHLO-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(5-methyl-1H-pyrazol-3-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC(=NN2)C HAOFFINFSLFHLO-QGZVFWFLSA-N 0.000 claims 2
ATHWMBCGYAOIPF-JOCHJYFZSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(5-phenyl-1H-pyrazol-3-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC(=NN2)C2=CC=CC=C2 ATHWMBCGYAOIPF-JOCHJYFZSA-N 0.000 claims 2
PJKIRTFIEQIQSG-LJQANCHMSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(5-propan-2-yl-1H-pyrazol-3-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC(=NN2)C(C)C PJKIRTFIEQIQSG-LJQANCHMSA-N 0.000 claims 2
WUVBGPVCSCCXSP-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[2-(methanesulfonamido)ethylamino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCNS(=O)(=O)C WUVBGPVCSCCXSP-QGZVFWFLSA-N 0.000 claims 2
HEEKQINZDCAHFU-XMMPIXPASA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[4-(1-methylpyrazol-4-yl)anilino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC=C(C=C2)C=2C=NN(C2)C HEEKQINZDCAHFU-XMMPIXPASA-N 0.000 claims 2
YRWRZGYJXFJFKY-OAQYLSRUSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[4-(1-methyltetrazol-5-yl)anilino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC=C(C=C2)C2=NN=NN2C YRWRZGYJXFJFKY-OAQYLSRUSA-N 0.000 claims 2
CXGAKWXRURKONL-BBTUJRGHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(1S,3S)-3-(2-hydroxypropan-2-yl)cyclopentyl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H]2C[C@H](CC2)C(C)(C)O CXGAKWXRURKONL-BBTUJRGHSA-N 0.000 claims 2
IAMRKUYIYATLPD-MAUKXSAKSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2S)-1-hydroxybutan-2-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H](CO)CC IAMRKUYIYATLPD-MAUKXSAKSA-N 0.000 claims 2
JNICTEJYEKCSES-YVEFUNNKSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2S)-2-fluoropropyl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC[C@H](C)F JNICTEJYEKCSES-YVEFUNNKSA-N 0.000 claims 2
NUFOOSVVQHATGS-XMSQKQJNSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R)-1-(5-methoxypyrimidin-2-yl)pyrrolidin-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2CN(CC2)C2=NC=C(C=N2)OC NUFOOSVVQHATGS-XMSQKQJNSA-N 0.000 claims 2
KYQPVSVBFIQZPH-WIYYLYMNSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R)-1-pyrimidin-2-ylpyrrolidin-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2CN(CC2)C2=NC=CC=N2 KYQPVSVBFIQZPH-WIYYLYMNSA-N 0.000 claims 2
MTTXTGBRZNIHCZ-FZKQIMNGSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R)-3-hydroxybutyl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC[C@@H](C)O MTTXTGBRZNIHCZ-FZKQIMNGSA-N 0.000 claims 2
UFEBJAKKJGACRF-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2,2,2-trifluoroethyl)pyrazol-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=NN(C=C2)CC(F)(F)F UFEBJAKKJGACRF-QGZVFWFLSA-N 0.000 claims 2
SDNQSRRFVIKFTI-GOSISDBHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(F)(F)F SDNQSRRFVIKFTI-GOSISDBHSA-N 0.000 claims 2
GUYXWNHBCOSVGP-HXUWFJFHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2-fluoro-2-methylpropyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(C)(C)F GUYXWNHBCOSVGP-HXUWFJFHSA-N 0.000 claims 2
JADNUYPQFVBDKN-HXUWFJFHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2-hydroxy-2-methylpropyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(C)(C)O JADNUYPQFVBDKN-HXUWFJFHSA-N 0.000 claims 2
LWODVMIIVMVQPY-HXUWFJFHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2-methoxyethyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCOC LWODVMIIVMVQPY-HXUWFJFHSA-N 0.000 claims 2
RZOOSRMHBKBNPE-HXUWFJFHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(3-fluoropropyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCCF RZOOSRMHBKBNPE-HXUWFJFHSA-N 0.000 claims 2
HTFWDVFSXSXTOX-JOCHJYFZSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(5-fluoropyrimidin-2-yl)piperidin-4-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CCN(CC2)C2=NC=C(C=N2)F HTFWDVFSXSXTOX-JOCHJYFZSA-N 0.000 claims 2
MEGITHDTOCAYJP-JOCHJYFZSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(oxan-4-yl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)C2CCOCC2 MEGITHDTOCAYJP-JOCHJYFZSA-N 0.000 claims 2
YEYRUNXUIDTNDD-HXUWFJFHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(oxetan-3-yl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)C2COC2 YEYRUNXUIDTNDD-HXUWFJFHSA-N 0.000 claims 2
BEKGOYBQXNJWKO-VVXJCHQESA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-methyl-3-(trideuteriomethoxy)butyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)OC([2H])([2H])[2H])F)C(=C2)NC(C)C BEKGOYBQXNJWKO-VVXJCHQESA-N 0.000 claims 2
QIIGOQNNKVBHKJ-GOSISDBHSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-morpholin-4-yl-3-oxopropyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(=O)N1CCOCC1)F)C(=C2)NC(C)C QIIGOQNNKVBHKJ-GOSISDBHSA-N 0.000 claims 2
NHXAGKWSWQZMSE-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-oxo-3-(propan-2-ylamino)propyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(=O)NC(C)C)F)C(=C2)NC(C)C NHXAGKWSWQZMSE-QGZVFWFLSA-N 0.000 claims 2
QWRXCTZYOGLYCU-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-3-(difluoromethoxy)-2-fluoro-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)OC(F)F)F)C(=C2)NC(C)C QWRXCTZYOGLYCU-QGZVFWFLSA-N 0.000 claims 2
GWWSQNZXPDSXKR-LJQANCHMSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-3-ethoxy-2-fluoro-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)OCC)F)C(=C2)NC(C)C GWWSQNZXPDSXKR-LJQANCHMSA-N 0.000 claims 2
KXZCEDGLILHLAT-KRWDZBQOSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2S)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@@H](C(C)(C)O)F)C(=C2)NC(C)C KXZCEDGLILHLAT-KRWDZBQOSA-N 0.000 claims 2
BHLSUAIRCCJKEP-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2S)-2-fluoro-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)C)F)C(=C2)NC(C)C BHLSUAIRCCJKEP-QGZVFWFLSA-N 0.000 claims 2
MVGRLQPXSNBSCQ-QGZVFWFLSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(3R)-1-methylsulfonylpiperidin-3-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)N[C@H]1CN(CCC1)S(=O)(=O)C)C(=C2)NC(C)C MVGRLQPXSNBSCQ-QGZVFWFLSA-N 0.000 claims 2
WVBMIDALLQHWNB-XLIONFOSSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(3R,6S)-6-(2-hydroxypropan-2-yl)oxan-3-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)N[C@H]1CO[C@@H](CC1)C(C)(C)O)C(=C2)NC(C)C WVBMIDALLQHWNB-XLIONFOSSA-N 0.000 claims 2
MVGRLQPXSNBSCQ-KRWDZBQOSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(3S)-1-methylsulfonylpiperidin-3-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)N[C@@H]1CN(CCC1)S(=O)(=O)C)C(=C2)NC(C)C MVGRLQPXSNBSCQ-KRWDZBQOSA-N 0.000 claims 2
RCRHSULXPAXQDS-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[1-(1-methylsulfonylazetidin-3-yl)pyrazol-4-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC=1C=NN(C1)C1CN(C1)S(=O)(=O)C)C(=C2)NC(C)C RCRHSULXPAXQDS-UHFFFAOYSA-N 0.000 claims 2
QSHWJGNNVHJYTH-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[1-(2,2-difluoroethyl)pyrazol-4-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC=1C=NN(C1)CC(F)F)C(=C2)NC(C)C QSHWJGNNVHJYTH-UHFFFAOYSA-N 0.000 claims 2
DLYNLVXDPMFCGF-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[1-(2-methylpropanoyl)piperidin-4-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1CCN(CC1)C(C(C)C)=O)C(=C2)NC(C)C DLYNLVXDPMFCGF-UHFFFAOYSA-N 0.000 claims 2
ONIAHQJPPBSJCQ-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[1-(methylsulfamoyl)piperidin-4-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1CCN(CC1)S(NC)(=O)=O)C(=C2)NC(C)C ONIAHQJPPBSJCQ-UHFFFAOYSA-N 0.000 claims 2
WWOPSYVLTKNGHF-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[1-(oxan-4-yl)pyrazol-4-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC=1C=NN(C1)C1CCOCC1)C(=C2)NC(C)C WWOPSYVLTKNGHF-UHFFFAOYSA-N 0.000 claims 2
LWNHBWIPQVTQIY-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[1-(oxetan-3-yl)pyrazol-4-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC=1C=NN(C1)C1COC1)C(=C2)NC(C)C LWNHBWIPQVTQIY-UHFFFAOYSA-N 0.000 claims 2
NDNMZMXCNNFKJU-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(1,1-dioxo-1,4-thiazinan-4-yl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCN1CCS(CC1)(=O)=O)C(=C2)NC(C)C NDNMZMXCNNFKJU-UHFFFAOYSA-N 0.000 claims 2
KRQLCXPRHUFIQM-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(1,4-dihydroxy-4-methylcyclohexyl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1(CCC(CC1)(C)O)O)C(=C2)NC(C)C KRQLCXPRHUFIQM-UHFFFAOYSA-N 0.000 claims 2
JXBOOVITOBTQKE-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(1-hydroxy-4-methoxycyclohexyl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1(CCC(CC1)OC)O)C(=C2)NC(C)C JXBOOVITOBTQKE-UHFFFAOYSA-N 0.000 claims 2
SWEFIBLGVPAYBS-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(1-hydroxycyclopentyl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1(CCCC1)O)C(=C2)NC(C)C SWEFIBLGVPAYBS-UHFFFAOYSA-N 0.000 claims 2
IYFWLBGKCWAFAD-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(1-methylpiperidin-4-yl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1CCN(CC1)C)C(=C2)NC(C)C IYFWLBGKCWAFAD-UHFFFAOYSA-N 0.000 claims 2
YAMNEMHESDNQKW-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(3-hydroxypyrrolidin-3-yl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1(CNCC1)O)C(=C2)NC(C)C YAMNEMHESDNQKW-UHFFFAOYSA-N 0.000 claims 2
KXYJRBVMSMHIMD-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(4,4-difluoro-1-hydroxycyclohexyl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1(CCC(CC1)(F)F)O)C(=C2)NC(C)C KXYJRBVMSMHIMD-UHFFFAOYSA-N 0.000 claims 2
PJZWVDKFRGJITA-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(4-fluorophenyl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1=CC=C(C=C1)F)C(=C2)NC(C)C PJZWVDKFRGJITA-UHFFFAOYSA-N 0.000 claims 2
GFVOJWJVWSJFRP-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(4-hydroxy-1-methylpiperidin-4-yl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1(CCN(CC1)C)O)C(=C2)NC(C)C GFVOJWJVWSJFRP-UHFFFAOYSA-N 0.000 claims 2
SDXFKVCZLVACQY-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(4-methoxyphenyl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1=CC=C(C=C1)OC)C(=C2)NC(C)C SDXFKVCZLVACQY-UHFFFAOYSA-N 0.000 claims 2
MMBAVGYEYRIAFQ-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(methanesulfonamido)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCNS(=O)(=O)C)C(=C2)NC(C)C MMBAVGYEYRIAFQ-UHFFFAOYSA-N 0.000 claims 2
GSHYBAHPKIUEPF-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(oxan-2-yl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1OCCCC1)C(=C2)NC(C)C GSHYBAHPKIUEPF-UHFFFAOYSA-N 0.000 claims 2
QQFOMKJAKMWEJW-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-(oxan-4-yl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1CCOCC1)C(=C2)NC(C)C QQFOMKJAKMWEJW-UHFFFAOYSA-N 0.000 claims 2
AQRRPAKMBWVNRL-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-[4-hydroxy-1-(oxetan-3-yl)piperidin-4-yl]ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1(CCN(CC1)C1COC1)O)C(=C2)NC(C)C AQRRPAKMBWVNRL-UHFFFAOYSA-N 0.000 claims 2
HJPBHGWPEGRBOF-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[2-fluoro-2-(oxan-4-yl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCC(C1CCOCC1)F)C(=C2)NC(C)C HJPBHGWPEGRBOF-UHFFFAOYSA-N 0.000 claims 2
SHXYRCGMACKPPB-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[3-(ethylamino)-3-oxopropyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC(=O)NCC)C(=C2)NC(C)C SHXYRCGMACKPPB-UHFFFAOYSA-N 0.000 claims 2
JBRGFSVAUPXTNV-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[3-(methanesulfonamido)-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC(C)(NS(=O)(=O)C)C)C(=C2)NC(C)C JBRGFSVAUPXTNV-UHFFFAOYSA-N 0.000 claims 2
NADOQKOZOYXMKW-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[4-(morpholin-4-ylmethyl)phenyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1=CC=C(C=C1)CN1CCOCC1)C(=C2)NC(C)C NADOQKOZOYXMKW-UHFFFAOYSA-N 0.000 claims 2
YNKVEYLLFYKWMV-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[5-(4-methoxypiperidin-1-yl)pyridin-2-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1=NC=C(C=C1)N1CCC(CC1)OC)C(=C2)NC(C)C YNKVEYLLFYKWMV-UHFFFAOYSA-N 0.000 claims 2
JAZQXACWPMKTTK-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[5-(4-methylpiperazin-1-yl)pyridin-2-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1=NC=C(C=C1)N1CCN(CC1)C)C(=C2)NC(C)C JAZQXACWPMKTTK-UHFFFAOYSA-N 0.000 claims 2
DAJLYWRJIGKABQ-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[5-[2-(dimethylamino)ethoxy]pyridin-2-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC1=NC=C(C=C1)OCCN(C)C)C(=C2)NC(C)C DAJLYWRJIGKABQ-UHFFFAOYSA-N 0.000 claims 2
YUZVULUCQVVWLJ-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[6-(4-methoxypiperidin-1-yl)pyridin-3-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC=1C=NC(=CC1)N1CCC(CC1)OC)C(=C2)NC(C)C YUZVULUCQVVWLJ-UHFFFAOYSA-N 0.000 claims 2
CLTVYGCREJLTQH-UHFFFAOYSA-N 6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[6-(dimethylamino)pyridin-3-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC=1C=NC(=CC1)N(C)C)C(=C2)NC(C)C CLTVYGCREJLTQH-UHFFFAOYSA-N 0.000 claims 2
GWSIODPFNQMNLA-JANGERMGSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-4-(4-fluorobutan-2-ylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)CCF GWSIODPFNQMNLA-JANGERMGSA-N 0.000 claims 2
LCMARHFRAQJUTM-LJQANCHMSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-4-(cyclobutylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CCC2 LCMARHFRAQJUTM-LJQANCHMSA-N 0.000 claims 2
KFSNDEVCMRLYMY-UHFFFAOYSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-4-(cyclopropylamino)-N-[2-(methanesulfonamido)ethyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NCCNS(=O)(=O)C)C(=C2)NC2CC2 KFSNDEVCMRLYMY-UHFFFAOYSA-N 0.000 claims 2
VEEJITCKDVNINW-LJQANCHMSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-4-[(1-fluorocyclobutyl)methylamino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC2(CCC2)F VEEJITCKDVNINW-LJQANCHMSA-N 0.000 claims 2
MADHTMRSFJHJCD-JLTOFOAXSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-4-[[(1R)-1-cyclopropylethyl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H](C)C2CC2 MADHTMRSFJHJCD-JLTOFOAXSA-N 0.000 claims 2
MADHTMRSFJHJCD-VBKZILBWSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-4-[[(1S)-1-cyclopropylethyl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H](C)C2CC2 MADHTMRSFJHJCD-VBKZILBWSA-N 0.000 claims 2
OKPRVZGPGATUGD-XODGURCBSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-4-[[(2S)-3-fluorobutan-2-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H](C)C(C)F OKPRVZGPGATUGD-XODGURCBSA-N 0.000 claims 2
KJGJBJAIRFHWIO-UHFFFAOYSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-(1-methylsulfonylpiperidin-4-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC1CCN(CC1)S(=O)(=O)C)C(=C2)NC(C)C KJGJBJAIRFHWIO-UHFFFAOYSA-N 0.000 claims 2
URLMSHFMEYHYSO-OALUTQOASA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(1S,3S)-3-(2-hydroxypropan-2-yl)cyclopentyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)N[C@@H]1C[C@H](CC1)C(C)(C)O)C(=C2)NC(C)C URLMSHFMEYHYSO-OALUTQOASA-N 0.000 claims 2
UOYZSRSFFJIIKF-OAQYLSRUSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2,3-difluoro-3-methylbutyl]-4-(3-hydroxyanilino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)F)F)C(=C2)NC2=CC(=CC=C2)O UOYZSRSFFJIIKF-OAQYLSRUSA-N 0.000 claims 2
SXTWKDYKXIWORC-JOCHJYFZSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(1H-indazol-5-ylamino)pyridine-3-carboxamide Chemical compound N1N=CC2=CC(=CC=C12)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1C=CC=2C1=NC=C(C2)C#N SXTWKDYKXIWORC-JOCHJYFZSA-N 0.000 claims 2
ANFPJFFCRKZASL-JANGERMGSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(3-hydroxybutylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCC(C)O ANFPJFFCRKZASL-JANGERMGSA-N 0.000 claims 2
UOGCOAYULLKVIC-JOCHJYFZSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(3-methoxyanilino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC(=CC=C2)OC UOGCOAYULLKVIC-JOCHJYFZSA-N 0.000 claims 2
GBZQUQDOFMXLHS-XMMPIXPASA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(4-imidazol-1-ylanilino)pyridine-3-carboxamide Chemical compound N1(C=NC=C1)C1=CC=C(C=C1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1C=CC=2C1=NC=C(C2)C#N GBZQUQDOFMXLHS-XMMPIXPASA-N 0.000 claims 2
ZVFUEIZYFYCWME-CAWMZFRYSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(4-methylpentan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)CC(C)C ZVFUEIZYFYCWME-CAWMZFRYSA-N 0.000 claims 2
PUZVBNZCFGDFPA-OAQYLSRUSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxan-4-ylmethylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC2CCOCC2 PUZVBNZCFGDFPA-OAQYLSRUSA-N 0.000 claims 2
QVMPRTWTYQYTFA-GOSISDBHSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2COC2 QVMPRTWTYQYTFA-GOSISDBHSA-N 0.000 claims 2
JFORGMDXGMQSIF-LJQANCHMSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-methylsulfonylazetidin-3-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CN(C2)S(=O)(=O)C JFORGMDXGMQSIF-LJQANCHMSA-N 0.000 claims 2
KCPSDEMRFWCWIV-AREMUKBSSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-phenylpiperidin-4-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CCN(CC2)C2=CC=CC=C2 KCPSDEMRFWCWIV-AREMUKBSSA-N 0.000 claims 2
SCRJXOPNOHNARJ-OAQYLSRUSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-propylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCC SCRJXOPNOHNARJ-OAQYLSRUSA-N 0.000 claims 2
QIGQFGPZPXMMSG-GOSISDBHSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(2-methylpyrazol-3-yl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2=CC=NN2C QIGQFGPZPXMMSG-GOSISDBHSA-N 0.000 claims 2
CQXIZBOVDKRCMT-IVAFLUGOSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[2-(3-methylmorpholin-4-yl)ethylamino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCN2C(COCC2)C CQXIZBOVDKRCMT-IVAFLUGOSA-N 0.000 claims 2
MRLMYJRGCXVAOQ-HSZRJFAPSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[3-(1H-imidazol-2-yl)anilino]pyridine-3-carboxamide Chemical compound N1C(=NC=C1)C=1C=C(C=CC1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1C=CC=2C1=NC=C(C2)C#N MRLMYJRGCXVAOQ-HSZRJFAPSA-N 0.000 claims 2
OXHZKOQFRVMXPC-HSZRJFAPSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[4-(1,2,4-triazol-1-yl)anilino]pyridine-3-carboxamide Chemical compound N1(N=CN=C1)C1=CC=C(C=C1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1C=CC=2C1=NC=C(C2)C#N OXHZKOQFRVMXPC-HSZRJFAPSA-N 0.000 claims 2
SRPMGPKURIQWID-UYAOXDASSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2R)-2-fluoro-3-oxo-3-(propan-2-ylamino)propyl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC[C@H](C(=O)NC(C)C)F SRPMGPKURIQWID-UYAOXDASSA-N 0.000 claims 2
CYZWJXNIOTTZDS-FZKQIMNGSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2R)-2-fluoropropyl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC[C@@H](C)F CYZWJXNIOTTZDS-FZKQIMNGSA-N 0.000 claims 2
ZJBVOZDIUPZVLN-SCLBCKFNSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2S)-1-hydroxypropan-2-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H](CO)C ZJBVOZDIUPZVLN-SCLBCKFNSA-N 0.000 claims 2
GXSDTVUVVZPZDW-GWGYHSHPSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2S)-3-hydroxy-5-methylhexan-2-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H](C)C(CC(C)C)O GXSDTVUVVZPZDW-GWGYHSHPSA-N 0.000 claims 2
PMQJTKQHVACTMZ-YLJYHZDGSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R)-1-(3,3,3-trifluoropropanoyl)pyrrolidin-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2CN(CC2)C(CC(F)(F)F)=O PMQJTKQHVACTMZ-YLJYHZDGSA-N 0.000 claims 2
HWJXGCYEYGOGCE-DENIHFKCSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R)-1-(5-fluoropyrimidin-2-yl)pyrrolidin-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2CN(CC2)C2=NC=C(C=N2)F HWJXGCYEYGOGCE-DENIHFKCSA-N 0.000 claims 2
NMHRLANGFQMVRW-YLJYHZDGSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R)-1-methylsulfonylpyrrolidin-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2CN(CC2)S(=O)(=O)C NMHRLANGFQMVRW-YLJYHZDGSA-N 0.000 claims 2
IFSGHUOXHSLSNT-VQIMIIECSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R)-oxolan-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2COCC2 IFSGHUOXHSLSNT-VQIMIIECSA-N 0.000 claims 2
JKBRSKQBVXMVNU-BHIYHBOVSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R,4S)-4-fluorooxolan-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H]2COC[C@H]2F JKBRSKQBVXMVNU-BHIYHBOVSA-N 0.000 claims 2
OYBSHMAQINZNFI-GUDVDZBRSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R,4S)-4-hydroxyoxolan-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H]2COC[C@H]2O OYBSHMAQINZNFI-GUDVDZBRSA-N 0.000 claims 2
IFSGHUOXHSLSNT-QFBILLFUSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3S)-oxolan-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H]2COCC2 IFSGHUOXHSLSNT-QFBILLFUSA-N 0.000 claims 2
RUTUXFGXSFRWFD-LJQANCHMSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(F)(F)F RUTUXFGXSFRWFD-LJQANCHMSA-N 0.000 claims 2
LTLBZIPENRWWHN-OAQYLSRUSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(5-fluoropyrimidin-2-yl)azetidin-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CN(C2)C2=NC=C(C=N2)F LTLBZIPENRWWHN-OAQYLSRUSA-N 0.000 claims 2
KPTDEDHZEHJTAW-QYGXFBIXSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[2-(1H-imidazol-5-yl)cyclopropyl]amino]pyridine-3-carboxamide Chemical compound N1C=NC(=C1)C1C(C1)NC1=CC(=NC=C1C(=O)NC[C@H](C(C)(C)O)F)N1C=CC=2C1=NC=C(C2)C#N KPTDEDHZEHJTAW-QYGXFBIXSA-N 0.000 claims 2
CRPCDRSYNCWGOQ-ORWMALAUSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[3-(hydroxymethyl)cyclohexyl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC(CCC2)CO CRPCDRSYNCWGOQ-ORWMALAUSA-N 0.000 claims 2
DDJPRVYMXFFEIW-LJQANCHMSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-methoxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)OC)F)C(=C2)NC(C)C DDJPRVYMXFFEIW-LJQANCHMSA-N 0.000 claims 2
MKRIABWYOGTFNN-ZCVQGDCRSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-methyl-3-(trideuteriomethoxy)butyl]-4-[[3-(hydroxymethyl)cyclohexyl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)OC([2H])([2H])[2H])F)C(=C2)NC2CC(CCC2)CO MKRIABWYOGTFNN-ZCVQGDCRSA-N 0.000 claims 2
DPPRLUQHAQZWIU-HXUWFJFHSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[(2R)-3-ethoxy-2-fluoro-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)OCC)F)C(=C2)NC(C)C DPPRLUQHAQZWIU-HXUWFJFHSA-N 0.000 claims 2
RQEQIZKLRBHQCU-UHFFFAOYSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[2-(1-hydroxycyclopentyl)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NCCC1(CCCC1)O)C(=C2)NC(C)C RQEQIZKLRBHQCU-UHFFFAOYSA-N 0.000 claims 2
NECVWZJWYPWQKL-UHFFFAOYSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NCC(=O)N1CCN(CC1)C)C(=C2)NC(C)C NECVWZJWYPWQKL-UHFFFAOYSA-N 0.000 claims 2
DVUSWHVFVDTUEL-UHFFFAOYSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[2-(methanesulfonamido)ethyl]-4-(oxan-4-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NCCNS(=O)(=O)C)C(=C2)NC2CCOCC2 DVUSWHVFVDTUEL-UHFFFAOYSA-N 0.000 claims 2
XIMLFSGWEOYRLI-UHFFFAOYSA-N 6-(5-cyanopyrrolo[2,3-b]pyridin-1-yl)-N-[2-(morpholin-4-ylsulfonylamino)ethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NCCNS(=O)(=O)N1CCOCC1)C(=C2)NC(C)C XIMLFSGWEOYRLI-UHFFFAOYSA-N 0.000 claims 2
LQZZTJHPZMCLIZ-OAHLLOKOSA-N 6-(6-amino-5-chloropyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound CC(C)NC1=CC(=NC=C1C(=O)NC[C@@H](F)C(C)(C)O)N1N=CC2=C1N=C(N)C(Cl)=C2 LQZZTJHPZMCLIZ-OAHLLOKOSA-N 0.000 claims 2
BUMZBVAIJDWMKD-MRXNPFEDSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(cyclopropylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC2)C#N BUMZBVAIJDWMKD-MRXNPFEDSA-N 0.000 claims 2
YKKRDCRLFSOWCJ-OAHLLOKOSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(ethylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC)C#N YKKRDCRLFSOWCJ-OAHLLOKOSA-N 0.000 claims 2
TZAGTUBYAYQIAL-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)-N-propylpyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NCCC)C(=C2)NC(C)C)C#N TZAGTUBYAYQIAL-UHFFFAOYSA-N 0.000 claims 2
NJOJKTFAIRXHCT-SJKOYZFVSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[(2R)-butan-2-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H](C)CC)C#N NJOJKTFAIRXHCT-SJKOYZFVSA-N 0.000 claims 2
NJOJKTFAIRXHCT-YVEFUNNKSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[(2S)-butan-2-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@@H](C)CC)C#N NJOJKTFAIRXHCT-YVEFUNNKSA-N 0.000 claims 2
DCUHNZGXNZPARS-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(1-cyanocyclopropyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC1(CC1)C#N)C(=C2)NC(C)C)C#N DCUHNZGXNZPARS-UHFFFAOYSA-N 0.000 claims 2
WMQQVROBVMSCDG-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(1-methylcyclopropyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC1(CC1)C)C(=C2)NC(C)C)C#N WMQQVROBVMSCDG-UHFFFAOYSA-N 0.000 claims 2
JMLLBPWPCVRYBT-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(2-cyclopropylethyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NCCC1CC1)C(=C2)NC(C)C)C#N JMLLBPWPCVRYBT-UHFFFAOYSA-N 0.000 claims 2
BOCJQRSYLIUISM-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(3-fluoro-3-methylbutyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NCCC(C)(C)F)C(=C2)NC(C)C)C#N BOCJQRSYLIUISM-UHFFFAOYSA-N 0.000 claims 2
BHSXDRPIWNYYLO-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(3-methylbutyl)-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NCCC(C)C)C(=C2)NC2COC2)C#N BHSXDRPIWNYYLO-UHFFFAOYSA-N 0.000 claims 2
VSTZGNLMEJBMRT-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-(3-methylbutyl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NCCC(C)C)C(=C2)NC(C)C)C#N VSTZGNLMEJBMRT-UHFFFAOYSA-N 0.000 claims 2
FNJOETBVWGWFGK-GFCCVEGCSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(1R)-1-cyclopropylethyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)N[C@H](C)C1CC1)C(=C2)NC(C)C)C#N FNJOETBVWGWFGK-GFCCVEGCSA-N 0.000 claims 2
DUJQELDSNGTVRC-MRXNPFEDSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2,3-difluoro-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)F)F)C(=C2)NC(C)C)C#N DUJQELDSNGTVRC-MRXNPFEDSA-N 0.000 claims 2
AGSJNZOVFNVYIF-MRXNPFEDSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C)C#N AGSJNZOVFNVYIF-MRXNPFEDSA-N 0.000 claims 2
QRPPVEMATFPXNI-MRXNPFEDSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCC)C#N QRPPVEMATFPXNI-MRXNPFEDSA-N 0.000 claims 2
PJZOHHTUBQMILL-QGZVFWFLSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(3-fluoro-3-methylbutyl)amino]pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCC(C)(C)F)C#N PJZOHHTUBQMILL-QGZVFWFLSA-N 0.000 claims 2
XPZSXTHHZAXAFE-BDJLRTHQSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2R)-2-fluoropropyl]amino]pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC[C@@H](C)F)C#N XPZSXTHHZAXAFE-BDJLRTHQSA-N 0.000 claims 2
XPZSXTHHZAXAFE-MEDUHNTESA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(2S)-2-fluoropropyl]amino]pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC[C@H](C)F)C#N XPZSXTHHZAXAFE-MEDUHNTESA-N 0.000 claims 2
JCXRWBZUJDOEIS-LLVKDONJSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[(2R)-2-fluoropropyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@@H](C)F)C(=C2)NC(C)C)C#N JCXRWBZUJDOEIS-LLVKDONJSA-N 0.000 claims 2
GETBHCJTWVJGRH-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-[[2-(2-hydroxypropan-2-yl)cyclopropyl]methyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NCC1C(C1)C(C)(C)O)C(=C2)NC(C)C)C#N GETBHCJTWVJGRH-UHFFFAOYSA-N 0.000 claims 2
PPYTUSPPPLLRKK-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-butyl-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NCCCC)C(=C2)NC2COC2)C#N PPYTUSPPPLLRKK-UHFFFAOYSA-N 0.000 claims 2
CSKMBNXVCYTKAN-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-cyclohexyl-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC1CCCCC1)C(=C2)NC(C)C)C#N CSKMBNXVCYTKAN-UHFFFAOYSA-N 0.000 claims 2
VDJZZJIONAFBHQ-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-cyclopent-2-en-1-yl-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC1C=CCC1)C(=C2)NC(C)C)C#N VDJZZJIONAFBHQ-UHFFFAOYSA-N 0.000 claims 2
PQVIAUWKCYWRRR-UHFFFAOYSA-N 6-(6-amino-5-cyanopyrazolo[3,4-b]pyridin-1-yl)-N-methyl-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=C(C=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC)C(=C2)NC(C)C)C#N PQVIAUWKCYWRRR-UHFFFAOYSA-N 0.000 claims 2
PDFAZRDERGCQGV-CYBMUJFWSA-N 6-(6-aminopyrazolo[3,4-d]pyrimidin-1-yl)-4-(ethylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound NC1=NC=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC PDFAZRDERGCQGV-CYBMUJFWSA-N 0.000 claims 2
WSVZCYLWHXLJLL-CQSZACIVSA-N 6-(6-aminopyrazolo[3,4-d]pyrimidin-1-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound NC1=NC=C2C(=N1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C WSVZCYLWHXLJLL-CQSZACIVSA-N 0.000 claims 2
LNYZGGNVNXQBIV-GOSISDBHSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-4-[(1-ethylpyrazol-4-yl)amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC LNYZGGNVNXQBIV-GOSISDBHSA-N 0.000 claims 2
KSECOOSTCYCUCK-QGZVFWFLSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-[(2R)-2,3-difluoro-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)F)F)C(=C2)NC=2C=NN(C2)CC(F)F KSECOOSTCYCUCK-QGZVFWFLSA-N 0.000 claims 2
LIVDLWMNPCRETG-QGZVFWFLSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(F)F LIVDLWMNPCRETG-QGZVFWFLSA-N 0.000 claims 2
VQXUMABIUJJDCW-LJQANCHMSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-4-[[1-(2-cyanoethyl)pyrazol-4-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCC#N VQXUMABIUJJDCW-LJQANCHMSA-N 0.000 claims 2
MVWHQECEJRYEAB-MRXNPFEDSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2COC2 MVWHQECEJRYEAB-MRXNPFEDSA-N 0.000 claims 2
IUYGKDGPFQWAKO-MRXNPFEDSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C IUYGKDGPFQWAKO-MRXNPFEDSA-N 0.000 claims 2
IWTYPMSTOHQGEZ-QGZVFWFLSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-methylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)C IWTYPMSTOHQGEZ-QGZVFWFLSA-N 0.000 claims 2
UQTCXTXYGIKLJR-LJQANCHMSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-propan-2-ylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)C(C)C UQTCXTXYGIKLJR-LJQANCHMSA-N 0.000 claims 2
XMTNGFDBIGCVGI-LJQANCHMSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-propylpyrazol-4-yl)amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCC XMTNGFDBIGCVGI-LJQANCHMSA-N 0.000 claims 2
FRJLFEGHBHXIJT-QGZVFWFLSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(F)(F)F FRJLFEGHBHXIJT-QGZVFWFLSA-N 0.000 claims 2
YBQYWOIIJLUPKC-LJQANCHMSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(2-methoxyethyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCOC YBQYWOIIJLUPKC-LJQANCHMSA-N 0.000 claims 2
VUFUZVVTFSRXGR-LJQANCHMSA-N 6-(6-chloroimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[1-(3-fluoropropyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound ClC=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CCCF VUFUZVVTFSRXGR-LJQANCHMSA-N 0.000 claims 2
NBPPZDZNZRNBFM-GOSISDBHSA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-4-(cyclobutylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CCC2 NBPPZDZNZRNBFM-GOSISDBHSA-N 0.000 claims 2
UINBHVIPJXVCOG-QGZVFWFLSA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-4-(cyclopropylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CC2 UINBHVIPJXVCOG-QGZVFWFLSA-N 0.000 claims 2
CFDSZFWTBPLQEV-MRXNPFEDSA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-4-(ethylamino)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCC CFDSZFWTBPLQEV-MRXNPFEDSA-N 0.000 claims 2
MGMYLXLTGWUIKG-GOSISDBHSA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-[(2R)-2,3-difluoro-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)F)F)C(=C2)NC=2C=NN(C2)CC(F)F MGMYLXLTGWUIKG-GOSISDBHSA-N 0.000 claims 2
CQYPKAPZTBBJRA-GOSISDBHSA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(F)F CQYPKAPZTBBJRA-GOSISDBHSA-N 0.000 claims 2
PXFOANHIEFZVFA-YBMSBYLISA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-4-[[1-[2-(difluoromethoxy)propyl]pyrazol-4-yl]amino]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC=2C=NN(C2)CC(C)OC(F)F PXFOANHIEFZVFA-YBMSBYLISA-N 0.000 claims 2
MRVFOEHIOCTZJG-QGZVFWFLSA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2,3-difluoro-3-methylbutyl]-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)F)F)C(=C2)NC2COC2 MRVFOEHIOCTZJG-QGZVFWFLSA-N 0.000 claims 2
CXCOOSRUINXXKI-QGZVFWFLSA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2,3-difluoro-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)F)F)C(=C2)NC(C)C CXCOOSRUINXXKI-QGZVFWFLSA-N 0.000 claims 2
IODDMZNGSTYTSY-LJQANCHMSA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxan-4-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CCOCC2 IODDMZNGSTYTSY-LJQANCHMSA-N 0.000 claims 2
ZGUNYMKUAYUFIJ-QGZVFWFLSA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2COC2 ZGUNYMKUAYUFIJ-QGZVFWFLSA-N 0.000 claims 2
KSFIUOTUFLLVFV-QGZVFWFLSA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NCCC KSFIUOTUFLLVFV-QGZVFWFLSA-N 0.000 claims 2
MJXXCJSHXMMQHI-QGZVFWFLSA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[(1-methylcyclopropyl)amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2(CC2)C MJXXCJSHXMMQHI-QGZVFWFLSA-N 0.000 claims 2
WRYUYIISGCJXNK-RDTXWAMCSA-N 6-(6-cyanoimidazo[4,5-b]pyridin-3-yl)-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-[[(3R)-oxolan-3-yl]amino]pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(C=N2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)N[C@H]2COCC2 WRYUYIISGCJXNK-RDTXWAMCSA-N 0.000 claims 2
MPLAGAZWVMTNAA-MRXNPFEDSA-N 6-[5-(difluoromethyl)pyrazolo[3,4-b]pyridin-1-yl]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound FC(C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C)F MPLAGAZWVMTNAA-MRXNPFEDSA-N 0.000 claims 2
YRCMXTKNSXAIGF-OAQYLSRUSA-N 6-[5-[(cyclopropanecarbonylamino)methyl]pyrrolo[2,3-b]pyridin-1-yl]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C1(CC1)C(=O)NCC=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C YRCMXTKNSXAIGF-OAQYLSRUSA-N 0.000 claims 2
RZOJPJGVNNWNAJ-JOCHJYFZSA-N 6-[5-[(diethylcarbamoylamino)methyl]pyrrolo[2,3-b]pyridin-1-yl]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(C)N(C(NCC=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C)=O)CC RZOJPJGVNNWNAJ-JOCHJYFZSA-N 0.000 claims 2
KWWCDLYQMPRRCJ-XMMPIXPASA-N 6-[5-[[(2-cyclopentylacetyl)amino]methyl]pyrrolo[2,3-b]pyridin-1-yl]-N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C1(CCCC1)CC(=O)NCC=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C KWWCDLYQMPRRCJ-XMMPIXPASA-N 0.000 claims 2
GJRZXKQLHHXMSF-OTOKDRCRSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(2-morpholin-4-ylpropylamino)-6-pyrrolo[2,3-d]pyrimidin-7-ylpyridine-3-carboxamide Chemical compound F[C@H](CNC(C1=CN=C(C=C1NCC(C)N1CCOCC1)N1C=CC2=C1N=CN=C2)=O)C(C)(C)O GJRZXKQLHHXMSF-OTOKDRCRSA-N 0.000 claims 2
LWCBLKJOTKQQAP-OAQYLSRUSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-4-(propan-2-ylamino)-6-[5-[(propylcarbamoylamino)methyl]pyrrolo[2,3-b]pyridin-1-yl]pyridine-3-carboxamide Chemical compound F[C@H](CNC(C1=CN=C(C=C1NC(C)C)N1C=CC=2C1=NC=C(C2)CNC(=O)NCCC)=O)C(C)(C)O LWCBLKJOTKQQAP-OAQYLSRUSA-N 0.000 claims 2
KVRIQDQUDMYPLM-KPMSDPLLSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-(5-fluoropyrazolo[3,4-b]pyridin-1-yl)-4-(oxan-3-ylamino)pyridine-3-carboxamide Chemical compound FC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2COCCC2 KVRIQDQUDMYPLM-KPMSDPLLSA-N 0.000 claims 2
PIVNBIICPHCZGP-GOSISDBHSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-(5-fluoropyrazolo[3,4-b]pyridin-1-yl)-4-(oxan-4-ylamino)pyridine-3-carboxamide Chemical compound FC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2CCOCC2 PIVNBIICPHCZGP-GOSISDBHSA-N 0.000 claims 2
TXZRSXTWLLARGE-MRXNPFEDSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-(5-fluoropyrazolo[3,4-b]pyridin-1-yl)-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound FC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC2COC2 TXZRSXTWLLARGE-MRXNPFEDSA-N 0.000 claims 2
JKBFVARDLBFPLQ-MRXNPFEDSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-(5-fluoropyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound FC=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C JKBFVARDLBFPLQ-MRXNPFEDSA-N 0.000 claims 2
SVARHBJSSWOWDB-QGZVFWFLSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-(5-fluoropyrrolo[2,3-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound FC=1C=C2C(=NC1)N(C=C2)C2=NC=C(C(=O)NC[C@H](C(C)(C)O)F)C(=C2)NC(C)C SVARHBJSSWOWDB-QGZVFWFLSA-N 0.000 claims 2
XEPBHIZHBWPKBV-QZTJIDSGSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-[2-[[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]amino]purin-9-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound F[C@H](CNC(C1=CN=C(C=C1NC(C)C)N1C2=NC(=NC=C2N=C1)NC[C@H](C(C)(C)O)F)=O)C(C)(C)O XEPBHIZHBWPKBV-QZTJIDSGSA-N 0.000 claims 2
LWHXZWSOYVKXNL-OAQYLSRUSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-[5-[(3-methylbutanoylamino)methyl]pyrazolo[3,4-b]pyridin-1-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound F[C@H](CNC(C1=CN=C(C=C1NC(C)C)N1N=CC=2C1=NC=C(C2)CNC(CC(C)C)=O)=O)C(C)(C)O LWHXZWSOYVKXNL-OAQYLSRUSA-N 0.000 claims 2
QBMNOAIUJKEPFH-AVKWCDSFSA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-[5-[(oxolane-3-carbonylamino)methyl]pyrrolo[2,3-b]pyridin-1-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound F[C@H](CNC(C1=CN=C(C=C1NC(C)C)N1C=CC=2C1=NC=C(C2)CNC(=O)C2COCC2)=O)C(C)(C)O QBMNOAIUJKEPFH-AVKWCDSFSA-N 0.000 claims 2
XPHVKHKGHVMHIV-RUZDIDTESA-N N-[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]-6-[5-[[(2-phenylacetyl)amino]methyl]pyrrolo[2,3-b]pyridin-1-yl]-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound F[C@H](CNC(C1=CN=C(C=C1NC(C)C)N1C=CC=2C1=NC=C(C2)CNC(CC2=CC=CC=C2)=O)=O)C(C)(C)O XPHVKHKGHVMHIV-RUZDIDTESA-N 0.000 claims 2
WAGUKAVZXHZKNL-UHFFFAOYSA-N N-[2-[1-(2-cyanoacetyl)piperidin-4-yl]ethyl]-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1CCN(CC1)C(CC#N)=O)C(=C2)NC(C)C WAGUKAVZXHZKNL-UHFFFAOYSA-N 0.000 claims 2
XFNZWCUQHVEBMT-UHFFFAOYSA-N N-[2-[4-[bis(methylsulfonyl)amino]phenyl]ethyl]-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=O)NCCC1=CC=C(C=C1)N(S(=O)(=O)C)S(=O)(=O)C)C(=C2)NC(C)C XFNZWCUQHVEBMT-UHFFFAOYSA-N 0.000 claims 2
LMPUYPSDCKNZTF-UHFFFAOYSA-N N-butyl-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(oxetan-3-ylamino)pyridine-3-carboxamide Chemical compound C(CCC)NC(C1=CN=C(C=C1NC1COC1)N1N=CC=2C1=NC=C(C2)C#N)=O LMPUYPSDCKNZTF-UHFFFAOYSA-N 0.000 claims 2
QVXKELIRLNDKDF-UHFFFAOYSA-N N-butyl-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-(propan-2-ylamino)pyridine-3-carboxamide Chemical compound C(CCC)NC(C1=CN=C(C=C1NC(C)C)N1N=CC=2C1=NC=C(C2)C#N)=O QVXKELIRLNDKDF-UHFFFAOYSA-N 0.000 claims 2
FJVZNHUZTQKPIR-UHFFFAOYSA-N N-tert-butyl-6-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-4-[[1-(2,2-difluoroethyl)pyrazol-4-yl]amino]pyridine-3-carboxamide Chemical compound C(C)(C)(C)NC(C1=CN=C(C=C1NC=1C=NN(C1)CC(F)F)N1N=CC=2C1=NC=C(C2)C#N)=O FJVZNHUZTQKPIR-UHFFFAOYSA-N 0.000 claims 2
VODRZVLYVPXQTO-LJQANCHMSA-N ethyl 3-[[2-(5-cyanopyrazolo[3,4-b]pyridin-1-yl)-5-[[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]carbamoyl]pyridin-4-yl]amino]azetidine-1-carboxylate Chemical compound C(#N)C=1C=C2C(=NC1)N(N=C2)C2=NC=C(C(=C2)NC2CN(C2)C(=O)OCC)C(NC[C@H](C(C)(C)O)F)=O VODRZVLYVPXQTO-LJQANCHMSA-N 0.000 claims 2
HJPUBYUTWJPTLY-HXUWFJFHSA-N ethyl N-[[1-[5-[[(2R)-2-fluoro-3-hydroxy-3-methylbutyl]carbamoyl]-4-(propan-2-ylamino)pyridin-2-yl]pyrrolo[2,3-b]pyridin-5-yl]methyl]carbamate Chemical compound F[C@H](CNC(=O)C=1C(=CC(=NC1)N1C=CC=2C1=NC=C(C2)CNC(OCC)=O)NC(C)C)C(C)(C)O HJPUBYUTWJPTLY-HXUWFJFHSA-N 0.000 claims 2
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Classifications

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Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
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Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
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Bioinformatics & Cheminformatics (AREA)
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Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Immunology (AREA)
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Biomedical Technology (AREA)
Rheumatology (AREA)
Pain & Pain Management (AREA)
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Dermatology (AREA)
Physical Education & Sports Medicine (AREA)
Transplantation (AREA)
Urology & Nephrology (AREA)
Orthopedic Medicine & Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Plural Heterocyclic Compounds (AREA)

AU2015204045A 2014-01-03 2015-01-02 Heteroaryl substituted nicotinamide compounds Abandoned AU2015204045A1 (en)

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KR (1)	KR20160101191A (es)
CN (1)	CN106061967B (es)
AR (1)	AR098991A1 (es)
AU (1)	AU2015204045A1 (es)
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JP6215338B2 (ja)	2012-11-08	2017-10-18	ブリストル−マイヤーズスクイブカンパニーＢｒｉｓｔｏｌ−ＭｙｅｒｓＳｑｕｉｂｂＣｏｍｐａｎｙ	キナーゼモジュレーターとして有用な二環式ヘテロ環置換ピリジル化合物
PE20150953A1 (es)	2012-11-08	2015-06-20	Bristol Myers Squibb Co	Compuestos de piridilo sustituidos con heteroarilo utiles como moduladores de cinasa
GB201311888D0 (en)	2013-07-03	2013-08-14	Glaxosmithkline Ip Dev Ltd	Novel compounds
GB201311891D0 (en)	2013-07-03	2013-08-14	Glaxosmithkline Ip Dev Ltd	Novel compound
ES2813875T3 (es) *	2014-01-01	2021-03-25	Medivation Tech Llc	Compuestos y procedimientos de uso
JP6720355B2 (ja) *	2015-06-24	2020-07-08	ブリストル−マイヤーズスクイブカンパニーＢｒｉｓｔｏｌ−ＭｙｅｒｓＳｑｕｉｂｂＣｏｍｐａｎｙ	ヘテロアリール置換のアミノピリジン化合物
CN107849039B (zh)	2015-06-24	2020-07-03	百时美施贵宝公司	经杂芳基取代的氨基吡啶化合物
EP3313844B1 (en) *	2015-06-24	2020-08-26	Bristol-Myers Squibb Company	Heteroaryl substituted aminopyridine compounds
GB201518456D0 (en) *	2015-10-19	2015-12-02	Galapagos Nv	Novel compounds and pharmaceutical compositions thereof for the treatment of inflammatory, autoimmune and/or proliferative diseases
WO2017133667A1 (en) *	2016-02-05	2017-08-10	Savira Pharmaceuticals Gmbh	Pyrimidine and pyridine derivatives and use in treatment, amelioration or prevention of influenza thereof
WO2017133657A1 (en) *	2016-02-05	2017-08-10	Savira Pharmaceuticals Gmbh	Pyridine and pyrimidine derivatives and their use in treatment, amelioration or prevention of influenza
WO2018005863A1 (en) *	2016-07-01	2018-01-04	G1 Therapeutics, Inc.	Pyrimidine-based compounds for the treatment of cancer
JOP20180011A1 (ar)	2017-02-16	2019-01-30	Gilead Sciences Inc	مشتقات بيرولو [1، 2-b]بيريدازين
JP7266576B2 (ja) *	2017-08-04	2023-04-28	ブリストル－マイヤーズスクイブカンパニー	［１，２，４］トリアゾロ［４，３－ａ］ピリジニル置換のインドール化合物
KR102616949B1 (ko)	2017-09-14	2023-12-22	다이이찌 산쿄 가부시키가이샤	고리형 구조를 갖는 화합물
AU2018338314A1 (en)	2017-09-22	2020-04-09	Kymera Therapeutics, Inc	Protein degraders and uses thereof
EP3684366A4 (en)	2017-09-22	2021-09-08	Kymera Therapeutics, Inc.	CRBN LIGANDS AND USES OF THE LATEST
KR20190043437A (ko)	2017-10-18	2019-04-26	씨제이헬스케어 주식회사	단백질 키나제 억제제로서의 헤테로고리 화합물
WO2019099926A1 (en)	2017-11-17	2019-05-23	Arvinas, Inc.	Compounds and methods for the targeted degradation of interleukin-1 receptor-associated kinase 4 polypeptides
WO2019111218A1 (en)	2017-12-08	2019-06-13	Cadila Healthcare Limited	Novel heterocyclic compounds as irak4 inhibitors
TW201927769A (zh) *	2017-12-18	2019-07-16	德商歌林達有限公司	經取代之吡咯啶醯胺ｉｉ
JP2021508703A (ja)	2017-12-26	2021-03-11	カイメラセラピューティクス，インコーポレイテッド	Ｉｒａｋ分解剤およびそれらの使用
EP3737666A4 (en)	2018-01-12	2022-01-05	Kymera Therapeutics, Inc.	PROTEIN DEGRADANTS AND USES THEREOF
EP3737675A4 (en)	2018-01-12	2022-01-05	Kymera Therapeutics, Inc.	CRBN LIGANDS AND THEIR USES
WO2019160915A1 (en)	2018-02-14	2019-08-22	Dana-Farber Cancer Institute, Inc.	Irak degraders and uses thereof
EP3817748A4 (en)	2018-07-06	2022-08-24	Kymera Therapeutics, Inc.	TRICYCLIC CRBN LIGANDS AND USES THEREOF
TWI721483B (zh)	2018-07-13	2021-03-11	美商基利科學股份有限公司	吡咯并[1,2-b]嗒𠯤衍生物
TWI727392B (zh) *	2018-08-13	2021-05-11	美商基利科學股份有限公司	噻二唑irak4抑制劑
SG11202105424PA (en)	2018-11-30	2021-06-29	Kymera Therapeutics Inc	Irak degraders and uses thereof
IL293917A (en)	2019-12-17	2022-08-01	Kymera Therapeutics Inc	Iraq joints and their uses
EP4076524A4 (en)	2019-12-17	2023-11-29	Kymera Therapeutics, Inc.	IRAQ DEGRADERS AND USES THEREOF
TW202210483A (zh)	2020-06-03	2022-03-16	美商凱麥拉醫療公司	Irak降解劑之結晶型
WO2023008973A1 (ko) *	2021-07-29	2023-02-02	프라비바이오 주식회사	신규 벤젠 유도체 및 이의 면역억제 관련 용도
TW202315632A (zh)	2021-08-18	2023-04-16	美商新銳思生物製藥股份有限公司	介白素-1受體相關激酶之雙官能降解劑及其治療用途

Family Cites Families (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7273868B2 (en) *	2000-04-28	2007-09-25	Tanabe Seiyaku Co., Ltd.	Pyrazine derivatives
ATE432929T1 (de)	2001-06-15	2009-06-15	Vertex Pharma	5-(2-aminopyrimidin-4-yl)benzisoxazole als proteinkinasehemmer
AUPR688101A0 (en)	2001-08-08	2001-08-30	Luminis Pty Limited	Protein domains and their ligands
GB0211019D0 (en)	2002-05-14	2002-06-26	Syngenta Ltd	Novel compounds
US7449456B2 (en)	2002-06-28	2008-11-11	Astellas Pharma, Inc.	Diaminopyrimidinecarboxamide derivative
BRPI0406809A (pt)	2003-01-17	2005-12-27	Warner Lambert Co	Heterociclos substituìdos de 2-aminopiridina como inibidores da proliferação celular
CA2531401A1 (en)	2003-07-10	2005-01-27	Neurogen Corporation	Substituted heterocyclic diarylamine analogues
GB0402653D0 (en)	2004-02-06	2004-03-10	Cyclacel Ltd	Compounds
US7521457B2 (en)	2004-08-20	2009-04-21	Boehringer Ingelheim International Gmbh	Pyrimidines as PLK inhibitors
FR2896503B1 (fr)	2006-01-23	2012-07-13	Aventis Pharma Sa	Nouveaux derives soufres d'uree cyclique, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de kinases
AU2008258508A1 (en)	2007-06-08	2008-12-11	Bayer Cropscience Ag	Fungicide heterocyclyl-pyrimidinyl-amino derivatives
WO2009046416A1 (en)	2007-10-05	2009-04-09	Targegen Inc.	Anilinopyrimidines as jak kinase inhibitors
EA021367B1 (ru)	2008-11-28	2015-06-30	Кова Компани, Лтд.	Производное пиридин-3-карбоксамида
CN102458402B (zh)	2009-06-12	2013-10-02	百时美施贵宝公司	用作激酶调节剂的烟酰胺化合物
JP5770198B2 (ja)	2009-10-30	2015-08-26	ヤンセンファーマシューティカエヌ．ベー．	オピオイド受容体調節因子としてのフェノキシ置換ピリミジン
KR20120130104A (ko)	2010-02-01	2012-11-28	닛뽕 케미파 가부시키가이샤	Ｇｐｒ119 작동약
CN103619854A (zh)	2011-04-29	2014-03-05	西奈山伊坎医学院	激酶抑制剂
US9074384B2 (en) *	2011-07-27	2015-07-07	Intex Recreation Corp.	Combined swimming pool ladder structure
WO2013106612A1 (en)	2012-01-13	2013-07-18	Bristol-Myers Squibb Company	Heterocyclic-substituted pyridyl compounds useful as kinase inhibitors
CN104254533B (zh)	2012-01-13	2017-09-08	百时美施贵宝公司	用作激酶抑制剂的噻唑或噻二唑取代的吡啶基化合物
ES2630705T3 (es)	2012-01-13	2017-08-23	Bristol-Myers Squibb Company	Compuestos de piridilo sustituidos con triazolilo útiles como inhibidores de cinasas
KR102233252B1 (ko)	2012-11-08	2021-03-26	브리스톨-마이어스 스큅 컴퍼니	ＩＬ-12, ＩＬ-23 및/또는 ＩＦＮα 반응의 조절제로서 유용한 알킬-아미드-치환된 피리딜 화합물
PE20150953A1 (es) *	2012-11-08	2015-06-20	Bristol Myers Squibb Co	Compuestos de piridilo sustituidos con heteroarilo utiles como moduladores de cinasa
JP6215338B2 (ja) *	2012-11-08	2017-10-18	ブリストル−マイヤーズスクイブカンパニーＢｒｉｓｔｏｌ−ＭｙｅｒｓＳｑｕｉｂｂＣｏｍｐａｎｙ	キナーゼモジュレーターとして有用な二環式ヘテロ環置換ピリジル化合物

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TN2016000271A1 (en)	2017-10-06
IL246474A0 (en)	2016-08-31
EP3089973A1 (en)	2016-11-09
PE20161292A1 (es)	2016-11-23
MX2016008723A (es)	2016-09-07
WO2015103453A1 (en)	2015-07-09
AR098991A1 (es)	2016-06-22
ES2804707T3 (es)	2021-02-09
UY35935A (es)	2015-06-30
KR20160101191A (ko)	2016-08-24
US20150191464A1 (en)	2015-07-09
CA2935329A1 (en)	2015-07-09
CN106061967B (zh)	2019-04-19
MA39162A1 (fr)	2017-12-29
CN106061967A (zh)	2016-10-26
US9169252B2 (en)	2015-10-27
JP2017501202A (ja)	2017-01-12
SG11201605340QA (en)	2016-07-28
PH12016501164A1 (en)	2016-08-15
TW201609693A (zh)	2016-03-16
EP3089973B1 (en)	2020-04-29
EA201691343A1 (ru)	2016-11-30
JP6475252B2 (ja)	2019-02-27
CL2016001706A1 (es)	2017-02-10

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